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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

Optical and ultrasound visualization of different types of lesions in 6% BSA polyacrylamide TMM phantoms. The 'cigar’-shaped lesions (a) are typically created through thermal mechanisms only. The 'tadpole’-shaped (b) and 'egg’-shaped (c) lesions on the other hand are created by acoustic cavitation activity in the prefocal region (the FUS ultrasound transducer was on the right side). This interpretation is supported by the fact that the cavitation-based lesions are more visible by ultrasound due to the enhanced echogenicity of these regions (reprinted with permission from [11]).
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Figure 1: Optical and ultrasound visualization of different types of lesions in 6% BSA polyacrylamide TMM phantoms. The 'cigar’-shaped lesions (a) are typically created through thermal mechanisms only. The 'tadpole’-shaped (b) and 'egg’-shaped (c) lesions on the other hand are created by acoustic cavitation activity in the prefocal region (the FUS ultrasound transducer was on the right side). This interpretation is supported by the fact that the cavitation-based lesions are more visible by ultrasound due to the enhanced echogenicity of these regions (reprinted with permission from [11]).

Mentions: Perhaps the most widely used in vitro method for testing FUS exposures are phantoms made from tissue-mimicking materials (TMMs) such as polyacrylamide hydrogels [11,15]. The phantoms are translucent, allowing thermal lesions to be visualized optically, in addition to being detectable with diagnostic ultrasound. Bovine serum albumin (BSA) is also added to these phantoms as a heat-sensitive protein and to increase the attenuation coefficient of the TMM. When heated sufficiently, the BSA denatures, creating the visible lesion. These phantoms can also be produced in any shape or size, depending on the container in which they are made. One disadvantage of these TMMs is that even when using relatively high concentrations of BSA, the attenuation coefficient is still well below that of normal tissue (where the attenuation coefficient is the most important tissue characteristic for the generation of heat [16]). Therefore, relatively greater levels of energy will be required to produce a thermal lesion when compared to a typical soft tissue [11]. Another disadvantage is that the formation of the lesions is an irreversible process; hence, the phantoms cannot be reused. The manner by which these phantoms can be employed is demonstrated in Figure 1.


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

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

Optical and ultrasound visualization of different types of lesions in 6% BSA polyacrylamide TMM phantoms. The 'cigar’-shaped lesions (a) are typically created through thermal mechanisms only. The 'tadpole’-shaped (b) and 'egg’-shaped (c) lesions on the other hand are created by acoustic cavitation activity in the prefocal region (the FUS ultrasound transducer was on the right side). This interpretation is supported by the fact that the cavitation-based lesions are more visible by ultrasound due to the enhanced echogenicity of these regions (reprinted with permission from [11]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Optical and ultrasound visualization of different types of lesions in 6% BSA polyacrylamide TMM phantoms. The 'cigar’-shaped lesions (a) are typically created through thermal mechanisms only. The 'tadpole’-shaped (b) and 'egg’-shaped (c) lesions on the other hand are created by acoustic cavitation activity in the prefocal region (the FUS ultrasound transducer was on the right side). This interpretation is supported by the fact that the cavitation-based lesions are more visible by ultrasound due to the enhanced echogenicity of these regions (reprinted with permission from [11]).
Mentions: Perhaps the most widely used in vitro method for testing FUS exposures are phantoms made from tissue-mimicking materials (TMMs) such as polyacrylamide hydrogels [11,15]. The phantoms are translucent, allowing thermal lesions to be visualized optically, in addition to being detectable with diagnostic ultrasound. Bovine serum albumin (BSA) is also added to these phantoms as a heat-sensitive protein and to increase the attenuation coefficient of the TMM. When heated sufficiently, the BSA denatures, creating the visible lesion. These phantoms can also be produced in any shape or size, depending on the container in which they are made. One disadvantage of these TMMs is that even when using relatively high concentrations of BSA, the attenuation coefficient is still well below that of normal tissue (where the attenuation coefficient is the most important tissue characteristic for the generation of heat [16]). Therefore, relatively greater levels of energy will be required to produce a thermal lesion when compared to a typical soft tissue [11]. Another disadvantage is that the formation of the lesions is an irreversible process; hence, the phantoms cannot be reused. The manner by which these phantoms can be employed is demonstrated in Figure 1.

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