Limits...
In vitro parameter optimization for spatial control of focused ultrasound ablation when using low boiling point phase-change nanoemulsions.

Puett C, Phillips LC, Sheeran PS, Dayton PA - J Ther Ultrasound (2013)

Bottom Line: Their presence lowers the power required to ablate tissue by high-intensity focused ultrasound (HIFU), potentially making it a safer option for a broader range of treatment sites.Changes in the vaporization field shape and location occurred on a continuum with increasing PSNE concentration and acoustic intensity.This demonstration of controllable enhancement using a PSNE that contained a volatile PFC component is another step toward developing phase-shift nanotechnology as a potential clinical tool to improve HIFU.

View Article: PubMed Central - HTML - PubMed

Affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 109 Mason Farm Road, 304 Taylor Hall, CB 7575, Chapel Hill NC 27599, USA.

ABSTRACT

Background: Phase-shift nanoemulsions (PSNEs) provide cavitation sites when the perfluorocarbon (PFC) nanodroplets (ND) are vaporized to microbubbles by acoustic energy. Their presence lowers the power required to ablate tissue by high-intensity focused ultrasound (HIFU), potentially making it a safer option for a broader range of treatment sites. However, spatial control over the ablation region can be problematic when cavitation is used to enhance heating. This study explored relationships between vaporization, ablation, and the PSNE concentration in vitro to optimize the acoustic intensity and insonation time required for spatially controlled ablation enhancement using a PSNE that included a volatile PFC component.

Methods: HIFU (continuous wave at 1 MHz; insonation times of 5, 10, 15, and 20 s; cool-down times of 2, 4, and 6 s; peak negative pressures of 2, 3, and 4 MPa) was applied to albumin-acrylamide gels containing PFC agents (1:1 mix of volatile decafluorobutane and more stable dodecafluoropentane at 10(5) to 10(8) PFC ND per milliliter) or agent-free controls. Vaporization fields (microbubble clouds) were imaged by conventional ultrasound, and ablation lesions were measured directly by calipers. Controlled ablation was defined as the production of 'cigar'-shaped lesions corresponding with the acoustic focal zone. This control was considered to be lost when ablation occurred in prefocal vaporization fields having a predominantly 'tadpole' or oblong shape.

Results: Changes in the vaporization field shape and location occurred on a continuum with increasing PSNE concentration and acoustic intensity. Working with the maximum concentration-intensity combinations resulting in controlled ablation demonstrated a dose-responsive relationship between insonation time and volumes of both the vaporization fields (approximately 20 to 240 mm(3)) and the ablation lesions (1 to 135 mm(3)) within them.

Conclusions: HIFU ablation was enhanced by this PSNE and could be achieved using intensities ≤650 W/cm(2). Although the ablation lesions were located within much larger microbubble clouds, optimum insonation times and intensities could be selected to achieve an ablation lesion of desired size and location for a given PSNE concentration. This demonstration of controllable enhancement using a PSNE that contained a volatile PFC component is another step toward developing phase-shift nanotechnology as a potential clinical tool to improve HIFU.

No MeSH data available.


Related in: MedlinePlus

Vaporization field (microbubble cloud) and ablation lesion images obtained after applying continuous wave HIFU. HIFU was applied at 1 MHz to albumin-acrylamide gel phantoms containing 5 × 105 PFC ND per milliliter. (A) This ultrasound image shows a cigar-shaped vaporization field generated after 20 s of HIFU at 650 W/cm2 (4 MPa). (B) These optical images show four opaque white ablation lesions located in each transparent gel phantom following the application of HIFU at 650 W/cm2 for 5, 10, 15 and 20 s. Larger lesions can be observed in phantoms treated with longer insonation times. (C) A single ablation lesion cut along its vertical axis, demonstrating the desired cigar shape.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4265949&req=5

Figure 1: Vaporization field (microbubble cloud) and ablation lesion images obtained after applying continuous wave HIFU. HIFU was applied at 1 MHz to albumin-acrylamide gel phantoms containing 5 × 105 PFC ND per milliliter. (A) This ultrasound image shows a cigar-shaped vaporization field generated after 20 s of HIFU at 650 W/cm2 (4 MPa). (B) These optical images show four opaque white ablation lesions located in each transparent gel phantom following the application of HIFU at 650 W/cm2 for 5, 10, 15 and 20 s. Larger lesions can be observed in phantoms treated with longer insonation times. (C) A single ablation lesion cut along its vertical axis, demonstrating the desired cigar shape.

Mentions: Albumin-acrylamide tissue-mimicking phantoms were prepared and formed into 10-mL frustums (top diameter, 3 cm; bottom diameter, 4.1 cm; height, 1.2 cm) containing various concentrations of the stock PSNE [9,25]. The PSNE was gently stirred into the degassed acrylamide solution prior to polymerization in the frustum mold by the addition of 1% v/v of 10% ammonium persulfate and 0.4% v/v tetramethylethylenediamine. These albumin-acrylamide gels have acoustic properties similar to biologic tissues. Based on the final albumin concentration in these gels (35%), its density was 995 kg/m3, and sound traveled within the gel at a speed of 1,543 m/s [25]. In these studies, HIFU was delivered at 1 MHz, and at this frequency, attenuation by the gel was 0.28 dB/cm [25]. Vaporization fields (microbubble clouds) within the phantoms can be imaged by ultrasound (Figure 1A). Furthermore, the initially transparent gel turns opaque white in regions where the albumin is denatured at temperatures above 60°C, allowing for direct visual measurement of the ablation lesions (Figure 1B,C).


In vitro parameter optimization for spatial control of focused ultrasound ablation when using low boiling point phase-change nanoemulsions.

Puett C, Phillips LC, Sheeran PS, Dayton PA - J Ther Ultrasound (2013)

Vaporization field (microbubble cloud) and ablation lesion images obtained after applying continuous wave HIFU. HIFU was applied at 1 MHz to albumin-acrylamide gel phantoms containing 5 × 105 PFC ND per milliliter. (A) This ultrasound image shows a cigar-shaped vaporization field generated after 20 s of HIFU at 650 W/cm2 (4 MPa). (B) These optical images show four opaque white ablation lesions located in each transparent gel phantom following the application of HIFU at 650 W/cm2 for 5, 10, 15 and 20 s. Larger lesions can be observed in phantoms treated with longer insonation times. (C) A single ablation lesion cut along its vertical axis, demonstrating the desired cigar shape.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4265949&req=5

Figure 1: Vaporization field (microbubble cloud) and ablation lesion images obtained after applying continuous wave HIFU. HIFU was applied at 1 MHz to albumin-acrylamide gel phantoms containing 5 × 105 PFC ND per milliliter. (A) This ultrasound image shows a cigar-shaped vaporization field generated after 20 s of HIFU at 650 W/cm2 (4 MPa). (B) These optical images show four opaque white ablation lesions located in each transparent gel phantom following the application of HIFU at 650 W/cm2 for 5, 10, 15 and 20 s. Larger lesions can be observed in phantoms treated with longer insonation times. (C) A single ablation lesion cut along its vertical axis, demonstrating the desired cigar shape.
Mentions: Albumin-acrylamide tissue-mimicking phantoms were prepared and formed into 10-mL frustums (top diameter, 3 cm; bottom diameter, 4.1 cm; height, 1.2 cm) containing various concentrations of the stock PSNE [9,25]. The PSNE was gently stirred into the degassed acrylamide solution prior to polymerization in the frustum mold by the addition of 1% v/v of 10% ammonium persulfate and 0.4% v/v tetramethylethylenediamine. These albumin-acrylamide gels have acoustic properties similar to biologic tissues. Based on the final albumin concentration in these gels (35%), its density was 995 kg/m3, and sound traveled within the gel at a speed of 1,543 m/s [25]. In these studies, HIFU was delivered at 1 MHz, and at this frequency, attenuation by the gel was 0.28 dB/cm [25]. Vaporization fields (microbubble clouds) within the phantoms can be imaged by ultrasound (Figure 1A). Furthermore, the initially transparent gel turns opaque white in regions where the albumin is denatured at temperatures above 60°C, allowing for direct visual measurement of the ablation lesions (Figure 1B,C).

Bottom Line: Their presence lowers the power required to ablate tissue by high-intensity focused ultrasound (HIFU), potentially making it a safer option for a broader range of treatment sites.Changes in the vaporization field shape and location occurred on a continuum with increasing PSNE concentration and acoustic intensity.This demonstration of controllable enhancement using a PSNE that contained a volatile PFC component is another step toward developing phase-shift nanotechnology as a potential clinical tool to improve HIFU.

View Article: PubMed Central - HTML - PubMed

Affiliation: Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, 109 Mason Farm Road, 304 Taylor Hall, CB 7575, Chapel Hill NC 27599, USA.

ABSTRACT

Background: Phase-shift nanoemulsions (PSNEs) provide cavitation sites when the perfluorocarbon (PFC) nanodroplets (ND) are vaporized to microbubbles by acoustic energy. Their presence lowers the power required to ablate tissue by high-intensity focused ultrasound (HIFU), potentially making it a safer option for a broader range of treatment sites. However, spatial control over the ablation region can be problematic when cavitation is used to enhance heating. This study explored relationships between vaporization, ablation, and the PSNE concentration in vitro to optimize the acoustic intensity and insonation time required for spatially controlled ablation enhancement using a PSNE that included a volatile PFC component.

Methods: HIFU (continuous wave at 1 MHz; insonation times of 5, 10, 15, and 20 s; cool-down times of 2, 4, and 6 s; peak negative pressures of 2, 3, and 4 MPa) was applied to albumin-acrylamide gels containing PFC agents (1:1 mix of volatile decafluorobutane and more stable dodecafluoropentane at 10(5) to 10(8) PFC ND per milliliter) or agent-free controls. Vaporization fields (microbubble clouds) were imaged by conventional ultrasound, and ablation lesions were measured directly by calipers. Controlled ablation was defined as the production of 'cigar'-shaped lesions corresponding with the acoustic focal zone. This control was considered to be lost when ablation occurred in prefocal vaporization fields having a predominantly 'tadpole' or oblong shape.

Results: Changes in the vaporization field shape and location occurred on a continuum with increasing PSNE concentration and acoustic intensity. Working with the maximum concentration-intensity combinations resulting in controlled ablation demonstrated a dose-responsive relationship between insonation time and volumes of both the vaporization fields (approximately 20 to 240 mm(3)) and the ablation lesions (1 to 135 mm(3)) within them.

Conclusions: HIFU ablation was enhanced by this PSNE and could be achieved using intensities ≤650 W/cm(2). Although the ablation lesions were located within much larger microbubble clouds, optimum insonation times and intensities could be selected to achieve an ablation lesion of desired size and location for a given PSNE concentration. This demonstration of controllable enhancement using a PSNE that contained a volatile PFC component is another step toward developing phase-shift nanotechnology as a potential clinical tool to improve HIFU.

No MeSH data available.


Related in: MedlinePlus