title: Low-frequency pulsed ultrasound in the nasal cavity and paranasal sinuses: a feasibility and distribution study.
abstract: BACKGROUND
  Bacterial biofilms have been implicated in refractory rhinosinusitis. Biofilms have been shown to respond to treatment with low-frequency ultrasound (LFU) therapy in vitro, and exposure to LFU has shown efficacy in wound repair and topical drug delivery in other fields. This preliminary study was designed to evaluate the safety and feasibility of LFU for use in the nasal cavity and paranasal sinuses.
  
  
  METHODS
  This was an experimental observational study. Six cadaver heads were used to deliver a mixture of Renografin and methylene blue solvent to the paranasal sinuses via LFU both before and after resident endoscopic sinus dissection. Sinus computed tomography (CT) scans of the cadaver heads were performed before and after mixture delivery, and blinded assessments were made for distribution to individual sinuses. Mucosa was harvested from 2 subsites to evaluate LFU-treated cadaver tissue.
  
  
  RESULTS
  Predissection, LFU delivered solution to 12 of 12 inferior and middle turbinates, 6 of 12 of the superior turbinates and ethmoid sinuses, and 1 of 12 maxillary sinuses as shown by contrast radiography. Postdissection, all heads showed delivery to the maxillary and sphenoid sinuses, with 8 of 12 sinus cavities showing delivery to the ethmoid region, and 4 of 11 to the frontal recess. Using hematoxylin and eosin (H&E) staining of tissue frozen sections, harvested tissue demonstrated no architectural damage to the mucosal layer from LFU exposure.
  
  
  CONCLUSIONS
  LFU appears to be capable of reliably delivering topical solution to the turbinates and ethmoid region preoperatively and to all sinuses, except the frontal, postoperatively. The nasal epithelium does not appear to be disrupted histologically from LFU at this time and distance. This data provides a foundation for a prospective human protocol studying the efficacy of this modality in the treatment of patients with chronic rhinosinusitis and biofilm formation.
authors.affiliation: Department of Otolaryngology, School of Medicine, Stanford University, Stanford, CA, USA.
authors.forename: Zara M
authors.initials: ZM
authors.lastname: Patel
authors.forename: Peter H
authors.initials: PH
authors.lastname: Hwang
authors.forename: Ary
authors.initials: A
authors.lastname: Chernomorsky
authors.forename: Dawn T
authors.initials: DT
authors.lastname: Bravo
authors.forename: Bryan L
authors.initials: BL
authors.lastname: Nguyen
authors.forename: Klementina
authors.initials: K
authors.lastname: Nesterova
authors.forename: Jayakar V
authors.initials: JV
authors.lastname: Nayak
mesh_terms: D018441:Biofilms; D002102:Cadaver; D003974:Diatrizoate Meglumine / Q000008:administration & dosage / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods; D004724:Endoscopy; D005240:Feasibility Studies; D006801:Humans; D008751:Methylene Blue / Q000008:administration & dosage / Q000493:pharmacokinetics; D009296:Nasal Cavity / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000601:surgery; D010256:Paranasal Sinuses / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000601:surgery; D011859:Radiography; D012008:Recurrence; D012220:Rhinitis / Q000175:diagnosis / Q000628:therapy*; D012852:Sinusitis / Q000175:diagnosis / Q000628:therapy*; D014055:Tomography, Emission-Computed; D014464:Ultrasonic Therapy / Q000379:methods*
chemical_list: D003974:Diatrizoate Meglumine; D008751:Methylene Blue