title: Experimental demonstration of passive acoustic imaging in the human skull cavity using CT-based aberration corrections.
abstract: OBJECTIVE
  Experimentally verify a previously described technique for performing passive acoustic imaging through an intact human skull using noninvasive, computed tomography (CT)-based aberration corrections Jones et al. [Phys. Med. Biol. 58, 4981-5005 (2013)].
  
  
  METHODS
  A sparse hemispherical receiver array (30 cm diameter) consisting of 128 piezoceramic discs (2.5 mm diameter, 612 kHz center frequency) was used to passively listen through ex vivo human skullcaps (n = 4) to acoustic emissions from a narrow-band fixed source (1 mm diameter, 516 kHz center frequency) and from ultrasound-stimulated (5 cycle bursts, 1 Hz pulse repetition frequency, estimated in situ peak negative pressure 0.11-0.33 MPa, 306 kHz driving frequency) Definity™ microbubbles flowing through a thin-walled tube phantom. Initial in vivo feasibility testing of the method was performed. The performance of the method was assessed through comparisons to images generated without skull corrections, with invasive source-based corrections, and with water-path control images.
  
  
  RESULTS
  For source locations at least 25 mm from the inner skull surface, the modified reconstruction algorithm successfully restored a single focus within the skull cavity at a location within 1.25 mm from the true position of the narrow-band source. The results obtained from imaging single bubbles are in good agreement with numerical simulations of point source emitters and the authors' previous experimental measurements using source-based skull corrections O'Reilly et al. [IEEE Trans. Biomed. Eng. 61, 1285-1294 (2014)]. In a rat model, microbubble activity was mapped through an intact human skull at pressure levels below and above the threshold for focused ultrasound-induced blood-brain barrier opening. During bursts that led to coherent bubble activity, the location of maximum intensity in images generated with CT-based skull corrections was found to deviate by less than 1 mm, on average, from the position obtained using source-based corrections.
  
  
  CONCLUSIONS
  Taken together, these results demonstrate the feasibility of using the method to guide bubble-mediated ultrasound therapies in the brain. The technique may also have application in ultrasound-based cerebral angiography.
authors.affiliation: Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Jones
authors.affiliation: Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada.
authors.forename: Meaghan A
authors.initials: MA
authors.lastname: O'Reilly
authors.affiliation: Physical Sciences Platform, Sunnybrook Research Institute, Toronto, Ontario M4N 3M5, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada; and Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, Ontario M5S 3G9, Canada.
authors.forename: Kullervo
authors.initials: K
authors.lastname: Hynynen
mesh_terms: D000465:Algorithms; D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging; D005240:Feasibility Studies; D006801:Humans; D057446:Hydrodynamics; D008297:Male; D045423:Microbubbles; D008954:Models, Biological; D019047:Phantoms, Imaging; D011312:Pressure; D017208:Rats, Wistar; D012886:Skull / Q000000981:diagnostic imaging*; D014057:Tomography, X-Ray Computed / Q000295:instrumentation / Q000379:methods*; D014464:Ultrasonic Therapy / Q000295:instrumentation / Q000379:methods*; D014463:Ultrasonography; D014867:Water
chemical_list: D014867:Water