Limits...
In vitro methods for evaluating therapeutic ultrasound exposures: present-day models and future innovations.

Alassaf A, Aleid A, Frenkel V - J Ther Ultrasound (2013)

Bottom Line: Each of these methods possesses characteristics that are well suited for various well-defined investigative goals.None, however, incorporate all the properties of real tissues, which include a 3D environment and live cells that may be maintained long-term post-treatment.Additional reporting is presented on the exciting and emerging field of 3D biological scaffolds, employing methods and materials adapted from tissue engineering.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Engineering, Catholic University of America, 620 Michigan Ave NE, Washington, DC 20064, USA.

ABSTRACT
Although preclinical experiments are ultimately required to evaluate new therapeutic ultrasound exposures and devices prior to clinical trials, in vitro experiments can play an important role in the developmental process. A variety of in vitro methods have been developed, where each of these has demonstrated their utility for various test purposes. These include inert tissue-mimicking phantoms, which can incorporate thermocouples or cells and ex vivo tissue. Cell-based methods have also been used, both in monolayer and suspension. More biologically relevant platforms have also shown utility, such as blood clots and collagen gels. Each of these methods possesses characteristics that are well suited for various well-defined investigative goals. None, however, incorporate all the properties of real tissues, which include a 3D environment and live cells that may be maintained long-term post-treatment. This review is intended to provide an overview of the existing application-specific in vitro methods available to therapeutic ultrasound investigators, highlighting their advantages and limitations. Additional reporting is presented on the exciting and emerging field of 3D biological scaffolds, employing methods and materials adapted from tissue engineering. This type of platform holds much promise for achieving more representative conditions of those found in vivo, especially important for the newest sphere of therapeutic applications, based on molecular changes that may be generated in response to non-destructive exposures.

No MeSH data available.


Related in: MedlinePlus

Experimental setup for investigating cavitation activity in agar gel tunnels. (left) A schematic representation of the setup showing the integration of the different elements that were used. (right) A photograph of the setup showing the gel, the FUS transducer, and the cavitation detector. All the components were in an acrylic tank filled with degassed water used for coupling. Microbubbles were injected into the tunnels just prior to the exposures (reprinted with permission from [36]).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4109267&req=5

Figure 4: Experimental setup for investigating cavitation activity in agar gel tunnels. (left) A schematic representation of the setup showing the integration of the different elements that were used. (right) A photograph of the setup showing the gel, the FUS transducer, and the cavitation detector. All the components were in an acrylic tank filled with degassed water used for coupling. Microbubbles were injected into the tunnels just prior to the exposures (reprinted with permission from [36]).

Mentions: So far, all the in vitro methods that have been discussed have involved attempts to reproduce, to one degree or another, the in vivo environment, where one or more biological components are included. Systems, however, have also been developed to investigate the effects of only a single and very specific characteristic, where actual biological components were not required. One example is the work of Sassaroli and Hynynen who carried out extensive investigations into the manner by which the diameter of a vessel will affect various aspects of acoustic cavitation activity, including the resonance frequency and the damping coefficient [36-38]. The importance of these studies was based on the principle that bubble activity under the geometrical confines of a blood vessel can be very different than that in free field (i.e., in an unconfined or infinite medium). In addition to mathematical modeling and simulations, the investigators also developed a number of experimental setups. These involved a FUS transducer directed at micron-sized tubes, at which a passive cavitation detector was also directed. Among the factors that were investigated was the relationship between the diameter of the tube and the acoustic pressure threshold for the induction of cavitation. Earlier studies used tubes made from silica and polyester [38]. More recently, they extended their investigations to using agar gels, in which tunnels were created to more realistically simulate small blood vessels in vivo[36]. This experimental setup appears in FigureĀ 4.


In vitro methods for evaluating therapeutic ultrasound exposures: present-day models and future innovations.

Alassaf A, Aleid A, Frenkel V - J Ther Ultrasound (2013)

Experimental setup for investigating cavitation activity in agar gel tunnels. (left) A schematic representation of the setup showing the integration of the different elements that were used. (right) A photograph of the setup showing the gel, the FUS transducer, and the cavitation detector. All the components were in an acrylic tank filled with degassed water used for coupling. Microbubbles were injected into the tunnels just prior to the exposures (reprinted with permission from [36]).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4109267&req=5

Figure 4: Experimental setup for investigating cavitation activity in agar gel tunnels. (left) A schematic representation of the setup showing the integration of the different elements that were used. (right) A photograph of the setup showing the gel, the FUS transducer, and the cavitation detector. All the components were in an acrylic tank filled with degassed water used for coupling. Microbubbles were injected into the tunnels just prior to the exposures (reprinted with permission from [36]).
Mentions: So far, all the in vitro methods that have been discussed have involved attempts to reproduce, to one degree or another, the in vivo environment, where one or more biological components are included. Systems, however, have also been developed to investigate the effects of only a single and very specific characteristic, where actual biological components were not required. One example is the work of Sassaroli and Hynynen who carried out extensive investigations into the manner by which the diameter of a vessel will affect various aspects of acoustic cavitation activity, including the resonance frequency and the damping coefficient [36-38]. The importance of these studies was based on the principle that bubble activity under the geometrical confines of a blood vessel can be very different than that in free field (i.e., in an unconfined or infinite medium). In addition to mathematical modeling and simulations, the investigators also developed a number of experimental setups. These involved a FUS transducer directed at micron-sized tubes, at which a passive cavitation detector was also directed. Among the factors that were investigated was the relationship between the diameter of the tube and the acoustic pressure threshold for the induction of cavitation. Earlier studies used tubes made from silica and polyester [38]. More recently, they extended their investigations to using agar gels, in which tunnels were created to more realistically simulate small blood vessels in vivo[36]. This experimental setup appears in FigureĀ 4.

Bottom Line: Each of these methods possesses characteristics that are well suited for various well-defined investigative goals.None, however, incorporate all the properties of real tissues, which include a 3D environment and live cells that may be maintained long-term post-treatment.Additional reporting is presented on the exciting and emerging field of 3D biological scaffolds, employing methods and materials adapted from tissue engineering.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Engineering, Catholic University of America, 620 Michigan Ave NE, Washington, DC 20064, USA.

ABSTRACT
Although preclinical experiments are ultimately required to evaluate new therapeutic ultrasound exposures and devices prior to clinical trials, in vitro experiments can play an important role in the developmental process. A variety of in vitro methods have been developed, where each of these has demonstrated their utility for various test purposes. These include inert tissue-mimicking phantoms, which can incorporate thermocouples or cells and ex vivo tissue. Cell-based methods have also been used, both in monolayer and suspension. More biologically relevant platforms have also shown utility, such as blood clots and collagen gels. Each of these methods possesses characteristics that are well suited for various well-defined investigative goals. None, however, incorporate all the properties of real tissues, which include a 3D environment and live cells that may be maintained long-term post-treatment. This review is intended to provide an overview of the existing application-specific in vitro methods available to therapeutic ultrasound investigators, highlighting their advantages and limitations. Additional reporting is presented on the exciting and emerging field of 3D biological scaffolds, employing methods and materials adapted from tissue engineering. This type of platform holds much promise for achieving more representative conditions of those found in vivo, especially important for the newest sphere of therapeutic applications, based on molecular changes that may be generated in response to non-destructive exposures.

No MeSH data available.


Related in: MedlinePlus