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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

Ablation lesion size as a function of the separation time of the HIFU treatment cycle. At intensities of (A) 140, (B) 390, and (C) 650 W/cm2, no statistically significant differences were observed between the volumes of the ablation lesions at separation times of 2, 4, and 6 s for any given insonation time (n ≥ 4, mean ± S.D.).
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Figure 7: Ablation lesion size as a function of the separation time of the HIFU treatment cycle. At intensities of (A) 140, (B) 390, and (C) 650 W/cm2, no statistically significant differences were observed between the volumes of the ablation lesions at separation times of 2, 4, and 6 s for any given insonation time (n ≥ 4, mean ± S.D.).

Mentions: Varying the ‘off’ or cool-down time that separated ablative insonation by 2, 4, and 6 s did not affect the volume of the ablation lesion for a given intensity and duration of insonation (Figure 7). However, a statistically significant dose responsive relationship (ANOVA, p < 0.001) was observed between the insonation time and the volume of the resulting ablation lesion (Figure 8). Averaging all measurements collected at a given insonation time demonstrated this relationship to be present even at the lowest acoustic intensity of 140 W/cm2 (PNP = 2 MPa), although the resulting ablation lesions were small and appeared inconsistently. On average, these ablation lesions measured just 4 mm3 after 20 s of HIFU, despite the fact that the phantoms contained the highest PFC concentration (1 × 107 ND per milliliter). This finding again demonstrated that 140 W/cm2 should be considered the minimum required intensity to achieve controllable ablation with this PSNE. When higher intensities were applied, the ablation lesions were significantly larger, even though the PFC concentrations were lower. Phantoms containing 2.5 × 106 ND per milliliter received HIFU at an intensity of 390 W/cm2 (PNP = 3 MPa). The resulting ablation lesions measured 8 mm3 after 5 s and 37 mm3 after 20 s. Applying an intensity of 650 W/cm2 (PNP = 4 MPa) to phantoms containing 5 × 105 nanodroplets per milliliter resulted in ablation lesions ranging from 19 to 135 mm3 with insonation times from 5 to 20 s.


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)

Ablation lesion size as a function of the separation time of the HIFU treatment cycle. At intensities of (A) 140, (B) 390, and (C) 650 W/cm2, no statistically significant differences were observed between the volumes of the ablation lesions at separation times of 2, 4, and 6 s for any given insonation time (n ≥ 4, mean ± S.D.).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 7: Ablation lesion size as a function of the separation time of the HIFU treatment cycle. At intensities of (A) 140, (B) 390, and (C) 650 W/cm2, no statistically significant differences were observed between the volumes of the ablation lesions at separation times of 2, 4, and 6 s for any given insonation time (n ≥ 4, mean ± S.D.).
Mentions: Varying the ‘off’ or cool-down time that separated ablative insonation by 2, 4, and 6 s did not affect the volume of the ablation lesion for a given intensity and duration of insonation (Figure 7). However, a statistically significant dose responsive relationship (ANOVA, p < 0.001) was observed between the insonation time and the volume of the resulting ablation lesion (Figure 8). Averaging all measurements collected at a given insonation time demonstrated this relationship to be present even at the lowest acoustic intensity of 140 W/cm2 (PNP = 2 MPa), although the resulting ablation lesions were small and appeared inconsistently. On average, these ablation lesions measured just 4 mm3 after 20 s of HIFU, despite the fact that the phantoms contained the highest PFC concentration (1 × 107 ND per milliliter). This finding again demonstrated that 140 W/cm2 should be considered the minimum required intensity to achieve controllable ablation with this PSNE. When higher intensities were applied, the ablation lesions were significantly larger, even though the PFC concentrations were lower. Phantoms containing 2.5 × 106 ND per milliliter received HIFU at an intensity of 390 W/cm2 (PNP = 3 MPa). The resulting ablation lesions measured 8 mm3 after 5 s and 37 mm3 after 20 s. Applying an intensity of 650 W/cm2 (PNP = 4 MPa) to phantoms containing 5 × 105 nanodroplets per milliliter resulted in ablation lesions ranging from 19 to 135 mm3 with insonation times from 5 to 20 s.

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