Darin Knaus

Nebulized Live-Attenuated Influenza Vaccine Provides Protection in Ferrets at a Reduced Dose

Live-attenuated influenza vaccine (LAIV) is delivered to vaccine recipients using a nasal spray syringe. LAIV delivered by this method is immunogenic at current doses; however, improvements in nasal delivery might allow for significant dose reduction. We investigated LAIV vaccination in ferrets using a high efficiency nebulizer designed for nasal delivery. LAIV nasal aerosol elicited high levels of serum neutralizing antibodies and protected ferrets from homologous virus challenge at conventional (10(7)TCID(50)) and significantly reduced (10(3)TCID(50)) doses. Aerosol LAIV also provided a significant level of subtype-specific cross-protection. These results demonstrate the dose-sparing potential of nebulizer-based nasal aerosol LAIV delivery.

System for laparoscopic tissue tracking

This paper describes the development of a laparoscopic tissue tracking system for use during minimally-invasive, image-guided abdominal surgery. The system is designed to measure organ position and shape to permit coregistration of preoperative, volumetric image data with the actual anatomy encountered during surgery. The laparoscopic tissue tracking system relies on projection of a scanned laser beam through a conventional laparoscope. The projected laser is then imaged using a second laparoscope oriented obliquely to the projecting laparoscope. Knowledge of the optical characteristics of the laparoscopes, along with their relative positions in space, allows determination of the three-dimensional coordinates of the illuminated point. Rapid localization permits tracking of tissue motion due to respiration or surgical manipulation. This paper provides a brief overview of the system, discusses system accuracy measured during laboratory testing, and shows data obtained from use of the system during surgery on an experimental animal

Tissue localization using endoscopic laser projection for image-guided surgery

Image-guided surgery has led to more accurate lesion targeting and improved outcomes in neurosurgery. However, adaptation of the technology to other forms of surgery has been slow largely due to difficulties in determining the position of anatomic landmarks within the surgical field. The ability to localize anatomic landmarks and provide real-time tracking of tissue motion without placing additional demands on the surgeon will facilitate image-guided surgery in a variety of clinical disciplines. Even approximate localization of anatomic landmarks would benefit many forms of surgery. For example, liver surgeons could visualize intraoperative locations on preoperative CT or MR scans to assist them in navigating through the complex hepatic vascular network. This paper describes the initial stages of development of an endoscopic localization system for use during minimally-invasive, image-guided abdominal surgery. The system projects a scanned laser beam through a conventional endoscope. The projected laser spot is then observed using a second endoscope orientated obliquely to the projecting endoscope. Knowledge of the optical geometry of the endoscopes, along with their relative positions in space, allows determination of the three-dimensional coordinates of the illuminated point. The ultimate accuracy of the system is dependent on the geometric relationship between the endoscopes, the ability to accurately measure the position of each endoscope, and careful calibration of the optics used to project the laser beam. We report a system design intended to support automated operation, methods and initial results of measurement of target points, and preliminary data characterizing the performance of the system.

Intranasal Deposition of Accuspray™ Aerosol in Anatomically Correct Models of 2-, 5-, and 12-Year-Old Children

BACKGROUND To our knowledge, quantification of intranasal deposition of aerosol generated by Accuspray(™) (AS) in children has never been published. We hypothesized that deposition would vary significantly with age and with placement of the device within, or outside, of the nostril. METHODS We tested these hypotheses in anatomically-correct physical models based on CT scans of 2-, 5-, and 12-year-old children with normal, intranasal airways. Models included a removable anterior nose (AN) with exterior facial features and interior nasal vestibule and nasal valve area and a main nasal airway (MNA), subdivided into upper (superior turbinates and olfactory area), middle (middle turbinates), and lower (inferior turbinates and nasopharynx) thirds. Aerosol was generated from distilled water admixed with (99m)technetium pertechnetate and administered during static airflow by AS inserted inside the right nostril (eight runs/model), or outside the right nostril (six runs/model). Mean aerosol Dv(50) ± standard deviation was 67.8 ± 24.7 μm. Deposition was quantified by 2D gamma scintigraphy and expressed as percentage of the emitted dose. RESULTS When placed inside the nostril, mean (± standard deviation) deposition within the MNA was significantly less in the 2-year-old, compared to the 5- and 12-year-old, averaging 46.8 ± 33.8% (AN:55.4 ± 29.9%), 75.4 ± 26.7% (AN:23.3 ± 13.6%), and 72.1 ± 18.5% (AN:25.8 ± 18.5%), respectively (p<0.05). When placed outside the nostril, MNA was significantly less in the 2- and 5-year-old compared to the 12-year-old, with 1.4 ± 2.5% (AN:69.7 ± 40.7%), 7.4 ± 9.0% (AN:77.8 ± 32.8%), and 21.1 ± 29.1% (AN:29.2 ± 19.3%), respectively (p<0.05). Deposition in the MNA of all age models was highest when AS was placed inside the nostril (p<0.05). Deposition in the lower third was significantly increased for the 5- and 12-year-old and in the middle third of the 5-year-old when AS was placed inside the nostril. CONCLUSIONS These results indicate that age and device placement play important roles in terms of intranasal deposition, when administering aerosol with Accuspray(™) to children.

Image-guided ex-vivo targeting accuracy using a laparoscopic tissue localization system

In image-guided surgery, discrete fiducials are used to determine a spatial registration between the location of surgical tools in the operating theater and the location of targeted subsurface lesions and critical anatomic features depicted in preoperative tomographic image data. However, the lack of readily localized anatomic landmarks has greatly hindered the use of image-guided surgery in minimally invasive abdominal procedures. To address these needs, we have previously described a laser-based system for localization of internal surface anatomy using conventional laparoscopes. During a procedure, this system generates a digitized, three-dimensional representation of visible anatomic surfaces in the abdominal cavity. This paper presents the results of an experiment utilizing an ex-vivo bovine liver to assess subsurface targeting accuracy achieved using our system. During the experiment, several radiopaque targets were inserted into the liver parenchyma. The location of each target was recorded using an optically-tracked insertion probe. The liver surface was digitized using our system, and registered with the liver surface extracted from post-procedure CT images. This surface-based registration was then used to transform the position of the inserted targets into the CT image volume. The target registration error (TRE) achieved using our surface-based registration (given a suitable registration algorithm initialization) was 2.4 mm ± 1.0 mm. A comparable TRE (2.6 mm ± 1.7 mm) was obtained using a registration based on traditional fiducial markers placed on the surface of the same liver. These results indicate the potential of fiducial-free, surface-to-surface registration for image-guided lesion targeting in minimally invasive abdominal surgery.