title: In vitro parameter optimization for spatial control of focused ultrasound ablation when using low boiling point phase-change nanoemulsions.
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.
authors.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.
authors.forename: Connor
authors.initials: C
authors.lastname: Puett
authors.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.
authors.forename: Linsey C
authors.initials: LC
authors.lastname: Phillips
authors.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.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Sheeran
authors.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.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Dayton
keywords: Decafluorobutane; High-Intensity Focused Ultrasound (HIFU); Nanodroplet; Perfluorocarbon; Phase-Shift; Tissue ablation; Vaporization