title: In vitro and in vivo evaluations of increased effective beam width for heat deposition using a split focus high intensity ultrasound (HIFU) transducer.
abstract: OBJECTIVE
  To develop a novel and efficient, in vitro method for characterizing temporal and spatial heat generation of focused ultrasound exposures, and evaluate this method to compare a split focus and conventional single focus high intensity focused ultrasound transducer.
  
  
  METHODS
  A HIFU tissue-mimicking phantom was validated by comparing respective temperature elevations generated in the phantoms and in murine tumors in vivo. The phantom was then used in combination with IR thermography to spatially and temporally characterize differences in low-level temperature elevation (e.g. 3-5 degrees C) produced by a single focus and split focus HIFU transducer, where the latter produces four simultaneous foci. In vivo experiments with heat sensitive liposomes containing doxorubicin were then carried out to determine if the larger beam width of the split focus transducer, compared to the single focus, could increase overall deployment of the drug from the liposome.
  
  
  RESULTS
  Temperature elevations generated in the HIFU phantom were not found to be different from those measured in vivo when compensating for disparities in attenuation coefficient and specific heat, and between the two transducers by increasing the energy deposition. Exposures with the split focus transducer provided significant increases in the area treated compared to the single focus, which then translated to significant increases in drug deposition in vivo.
  
  
  CONCLUSIONS
  Preliminary evidence was provided indicating the potential for using this novel technique for characterizing hyperthermia produced by focused ultrasound devices. Further development will be required for its suitability for correlating in vitro and in vivo outcomes.
authors.affiliation: Diagnostic Radiology Department, Clinical Center, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Pretesh R
authors.initials: PR
authors.lastname: Patel
authors.forename: Alfred
authors.initials: A
authors.lastname: Luk
authors.forename: Amirk
authors.initials: A
authors.lastname: Durrani
authors.forename: Sergio
authors.initials: S
authors.lastname: Dromi
authors.forename: Julian
authors.initials: J
authors.lastname: Cuesta
authors.forename: Mary
authors.initials: M
authors.lastname: Angstadt
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Dreher
authors.forename: Bradford J
authors.initials: BJ
authors.lastname: Wood
authors.forename: Victor
authors.initials: V
authors.lastname: Frenkel
mesh_terms: D000162:Acoustics; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000628:therapy*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006979:Hyperthermia, Induced / Q000379:methods*; D051379:Mice; D019042:Muscle Neoplasms / Q000628:therapy*; D019047:Phantoms, Imaging; D014159:Transducers; D014464:Ultrasonic Therapy / Q000295:instrumentation / Q000379:methods*; D014465:Ultrasonics
chemical_list: D004317:Doxorubicin