title: Deep Bleeder Acoustic Coagulation (DBAC)-part II: in vivo testing of a research prototype system.
abstract: BACKGROUND
  Deep Bleeder Acoustic Coagulation (DBAC) is an ultrasound image-guided high-intensity focused ultrasound (HIFU) method proposed to automatically detect and localize (D&L) and treat deep, bleeding, combat wounds in the limbs of soldiers. A prototype DBAC system consisting of an applicator and control unit was developed for testing on animals. To enhance control, and thus safety, of the ultimate human DBAC autonomous product system, a thermal coagulation strategy that minimized cavitation, boiling, and non-linear behaviors was used.
  
  
  METHODS
  The in vivo DBAC applicator design had four therapy tiles (Tx) and two 3D (volume) imaging probes (Ix) and was configured to be compatible with a porcine limb bleeder model developed in this research. The DBAC applicator was evaluated under quantitative test conditions (e.g., bleeder depths, flow rates, treatment time limits, and dose exposure time limits) in an in vivo study (final exam) comprising 12 bleeder treatments in three swine. To quantify blood flow rates, the "bleeder" targets were intact arterial branches, i.e., the superficial femoral artery (SFA) and a deep femoral artery (DFA). D&L identified, characterized, and targeted bleeders. The therapy sequence selected Tx arrays and determined the acoustic power and Tx beam steering, focus, and scan patterns. The user interface commands consisted of two buttons: "Start D&L" and "Start Therapy." Targeting accuracy was assessed by necropsy and histologic exams and efficacy (vessel coagulative occlusion) by angiography and histology.
  
  
  RESULTS
  The D&L process (Part I article, J Ther Ultrasound, 2015 (this issue)) executed fully in all cases in under 5 min and targeting evaluation showed 11 of 12 thermal lesions centered on the correct vessel subsection, with minimal damage to adjacent structures. The automated therapy sequence also executed properly, with select manual steps. Because the dose exposure time limit (t dose ≤ 30 s) was associated with nonefficacious treatment, 60-s dosing and dual-dosing was also pursued. Thrombogenic evidence (blood clotting) and collagen denaturation (vessel shrinkage) were found in necropsy and histologically in all targeted SFAs. Acute SFA reductions in blood flow (20-30 %) were achieved in one subject, and one partial and one complete vessel occlusion were confirmed angiographically. The complete occlusion case was achieved with a dual dose (90 s total exposure) with focal intensity ≈500 W/cm(2) (spatial average, temporal average).
  
  
  CONCLUSIONS
  While not meeting all in vivo objectives, the overall performance of the DBAC applicator was positive. In particular, D&L automation workflow was verified during each of the tests, with processing times well under specified (10 min) limits, and all bleeder branches were detected and localized. Further, gross necropsy and tissue examination confirmed that the HIFU thermal lesions were coincident with the target vessel locations in over 90 % of the multi-array dosing treatments. The SFA/DFA bleeder models selected, and the protocols used, were the most suitable practical model options for the given DBAC anatomical and bleeder requirements. The animal models were imperfect in some challenging aspects, including requiring tissue-mimicking material (TMM) standoffs to achieve deep target depths, thereby introducing device-tissue motion, with resultant imaging artifacts. The model "bleeders" involved intact vessels, which are subject to less efficient heating and coagulation cascade behaviors than true puncture injuries.
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA ; 8808 Points Dr. N.E., Yarrow Point, WA 98004 USA.
authors.forename: K Michael
authors.initials: KM
authors.lastname: Sekins
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Barnes
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA.
authors.forename: Liexiang
authors.initials: L
authors.lastname: Fan
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA.
authors.forename: Jerry D
authors.initials: JD
authors.lastname: Hopple
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Hsu
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA.
authors.forename: John
authors.initials: J
authors.lastname: Kook
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA.
authors.forename: Chi-Yin
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Maleke
authors.affiliation: Siemens Ultrasound Business Unit, 22010 S.E. 51st Street, Issaquah, WA 98029-1271 USA.
authors.forename: Xiaozheng Jenny
authors.initials: XJ
authors.lastname: Zeng
authors.affiliation: Siemens Corporate Research and Technology, 755 College Road East, Princeton, NJ 08540 USA.
authors.forename: Romain
authors.initials: R
authors.lastname: Moreau-Gobard
authors.affiliation: Siemens Corporate Research and Technology, 755 College Road East, Princeton, NJ 08540 USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Ahiekpor-Dravi
authors.affiliation: Siemens Corporate Research and Technology, 755 College Road East, Princeton, NJ 08540 USA.
authors.forename: Gareth
authors.initials: G
authors.lastname: Funka-Lea
authors.affiliation: ETN LLC, 1150 Guinda St., Palo Alto, CA 94301 USA.
authors.forename: John
authors.initials: J
authors.lastname: Eaton
authors.affiliation: ETN LLC, 1150 Guinda St., Palo Alto, CA 94301 USA.
authors.forename: Keith
authors.initials: K
authors.lastname: Wong
authors.affiliation: Siemens Corporate Research and Technology, 755 College Road East, Princeton, NJ 08540 USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Keneman
authors.affiliation: Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 013 NE 40th Street, Seattle, WA 98105-6698 USA.
authors.forename: Stuart B
authors.initials: SB
authors.lastname: Mitchell
authors.affiliation: Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 013 NE 40th Street, Seattle, WA 98105-6698 USA.
authors.forename: Barbrina
authors.initials: B
authors.lastname: Dunmire
authors.affiliation: Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 013 NE 40th Street, Seattle, WA 98105-6698 USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Kucewicz
authors.affiliation: Department of Veterinary Pathology, Texas A&M University, 4467 Veterinary Medical Science Building, College Station, TX 77843 USA.
authors.forename: Fred J
authors.initials: FJ
authors.lastname: Clubb
authors.affiliation: Texas Institute for Preclinical Studies (TIPS), Texas A&M University, College Station, TX 77843 USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Miller
authors.affiliation: Center for Industrial and Medical Ultrasound, Applied Physics Laboratory, University of Washington, 013 NE 40th Street, Seattle, WA 98105-6698 USA.
authors.forename: Lawrence A
authors.initials: LA
authors.lastname: Crum