Impact of acoustic airflow on intrasinus drug deposition: New insights into the vibrating mode and the optimal acoustic frequency to enhance the delivery of nebulized antibiotic.

AIM: We investigated the impact of vibrating acoustic airflow, the high frequency (f≥100 Hz) and the low frequency (f≤45 Hz) sound waves, on the enhancement of intrasinus drug deposition. METHODS: (81m)Kr-gas ventilation study was performed in a plastinated human cast with and without the addition of vibrating acoustic airflow. Similarly, intrasinus drug deposition in a nasal replica using gentamicin as a marker was studied with and without the superposition of different modes of acoustic airflow. RESULTS: Ventilation experiments demonstrate that no sinus ventilation was observed without acoustic airflow although sinus ventilation occurred whatever the modes of acoustic airflow applied. Intrasinus drug deposition experiments showed that the high frequency acoustic airflow led to 4-fold increase in gentamicin deposition into the left maxillary sinus and to 2-fold deposition increase into the right maxillary sinus. Besides, the low frequency acoustic airflow demonstrated a significant increase of 4-fold and 2-fold in the right and left maxillary sinuses, respectively. CONCLUSION: We demonstrated the benefit of different modes of vibrating acoustic airflow for maxillary sinus ventilation and intrasinus drug deposition. The degree of gentamicin deposition varies as a function of frequency of the vibrating acoustic airflow and the geometry of the ostia.

Hyperpolarized 83Kr MRI of lungs.

Hyperpolarized (hp) (83)Kr (spin I=9/2) is a promising gas-phase contrast agent that displays sensitivity to the surface chemistry, surface-to-volume ratio, and surface temperature of the surrounding environment. This proof-of-principle study demonstrates the feasibility of ex vivo hp (83)Kr magnetic resonance imaging (MRI) of lungs using natural abundance krypton gas (11.5% (83)Kr) and excised, but otherwise intact, rat lungs located within a custom designed ventilation chamber. Experiments comparing the (83)Kr MR signal intensity from lungs to that arising from a balloon with no internal structure inflated to the same volume with krypton gas mixture suggest that most of the observed signal originated from the alveoli and not merely the conducting airways. The (83)Kr longitudinal relaxation times in the rat lungs ranged from 0.7 to 3.7s but were reproducible for a given lung. Although the source of these variations was not explored in this work, hp (83)Kr T(1) differences may ultimately lead to a novel form of MRI contrast in lungs. The currently obtained 1200-fold signal enhancement for hp (83)Kr at 9.4T field strength is found to be 180 times below the theoretical upper limit.

Comparative analysis of different scintigraphic approaches to assess pulmonary ventilation.

A study was carried out to investigate the predictive value of 81-metastable-krypton (81mKr) distribution, high-size 99-metastable-technetium (99mTc) aerosol deposition and low-size 99mTc aerosol (Technegas) deposition on the pulmonary ventilation evaluated by 133-xenon (133Xe) lung scintigraphy, and to assess the correlation between the 81mKr distribution, the 99mTc aerosols deposition, and the respiratory parameters of patients with chronic obstructive pulmonary disease (COPD). Twenty COPD patients were included. The 81mKr, 133Xe, and 99mTc aerosol lung scintigraphies were successively carried out. The 81mKr distribution and 99mTc deposition were compared to the 133Xe distribution at equilibrium and to the 133Xe clearance. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 81mKr and Technegas lung scintigraphies to detect alterations in ventilation revealed by 133Xe were defined. The 81mKr distribution and 99mTc deposition according to respiratory parameters were described using a principal component analysis. Compared to 133Xe distribution, a significantly higher distribution of 81mKr in the upper parts of the lungs in the more severe patients (p = 0.05), a significantly higher deposition of Technegas in the lower parts of the lungs (p = 0.0008), and a significantly higher deposition in the central parts of the high-size 99mTc aerosol were observed (p = 0.0001). The PPV and the NPV were, respectively, 0.54 and 0.58 for 81mKr and 0.54 and 0.55 for Technegas. There was a significant negative correlation between 81mKr distribution and 133Xe clearance (p = 0.0001) between Technegas deposition and 133Xe clearance (p = 0.0007), and between 99mTc diethylene-triamino-penta-acetate (DTPA) deposition and 133Xe clearance (p = 0.001). Both the 81mKr peripheral distribution and Technegas peripheral deposition correlated negatively with increased obstruction, as measured by forced expiratory volume in 1 sec (FEV1). Peripheral deposition of the high-size 99mTc aerosol deposition correlated with the inspiration/expiration time ratio. In conclusion, 81mKr and 99mTc aerosols' lung scintigraphies do not reflect exactly the pulmonary ventilation as measured by 133Xe scintigraphy.

Hyperpolarized 3He MRI and 81mKr SPECT in chronic obstructive pulmonary disease.

PURPOSE: During recent years, magnetic resonance imaging (MRI) using hyperpolarised (HP) 3He gas has emerged as a promising new method for the imaging of lung ventilation. However, systematic comparisons with nuclear medicine techniques have not yet been performed. The aim of this study was to compare ventilation imaging methods in 26 patients with chronic obstructive pulmonary disease (COPD) and nine lung healthy volunteers. METHODS: HP 3He MRI, 81mKr single-photon emission computed tomography (SPECT), high-resolution computed tomography (HRCT) and pulmonary function tests were performed. The three scans were scored visually as percentage of non-ventilated/diseased lung, and a computer-based objective measure of the ventilated volume in HP 3He MRI and 81mKr SPECT and an emphysema index in HRCT were calculated. RESULTS: We found a good correlation between HP 3He MRI and 81mKr SPECT for both visual defect score (r=0.80, p<0.0001) and objective estimate of ventilation (r=0.45, p=0.0157). In addition, both scans were well correlated with reference methods for the diagnosis of emphysema (pulmonary function test and HRCT). The defect scores were largest on 81mKr SPECT (the score on HP 3He MRI was one-third less than that on 81mKr SPECT), but the difference was reduced after normalisation for different breathing depths (HP 3He MRI at total lung capacity; 81mKr SPECT at tidal breathing at functional residual capacity). CONCLUSION: HP 3He MRI provides detailed ventilation distribution images and defect scores are comparable on HP 3He MRI and 81mKr SPECT. Additionally, new insights into the regional pulmonary microstructure via the apparent diffusion coefficient measurements are provided by HP 3He MRI. HP 3He MRI is a promising new diagnostic tool for the assessment of ventilation distribution.

[Pulmonary distribution of 99mTc-technegas--a comparative study of radioactive inert gases].

99mTc-technegas (99mTc-gas), which consists of fine particles, is produced in carbon crucibles burned at 2500 degrees C. On this study, the particle size of 99mTc-gas was measured and the pulmonary distribution of 99mTc-gas was assessed in 28 patients with various pulmonary diseases. Most particles were 5-30 nm in diameter as determined by electron microscopy. In a clinical study, about 37 MBq of 99mTc-gas was inhaled three times during deep breathing in a sitting position. In a comparative study with radioactive inert gases (133Xe, 81mKr), 99mTc-gas showed a similar distribution to the inert gas in most patients, although some with obstructive disease showed hot spots in the lung fields. In patients with severe obstructive change, marked deposits of 99mTc-gas was noted in the central airways, but 99mTc-gas penetrated to the peripheral lung field. This result suggests that 99mTc-gas can be used to evaluate ventilatory function even in patients with chronic obstructive pulmonary diseases.

Quantitative comparison of regional distributions of inhaled Tc-99m DTPA aerosol and Kr-81m gas in coal miners' lungs.

Regional distributions of deposited Tc-99m diethylenetriamine pentaacetate aerosol (DPTA) and of Kr-81m were compared in the upright lungs of 22 coal miners with nonembolic pulmonary disease. Pixel-by-pixel distributions of Kr-81m and DPTA corrected for lung volume, as well as DTPA/Kr-81m ratios, were determined by computer analysis in each lung and plotted against lung position. DTPA was preferentially deposited in the basal regions of 36/44 lungs. In the same lungs, Kr-81m was preferentially distributed in the apical regions of 18 lungs, bilaterally in six subjects. Similar DTPA and Kr-81m regional distributions throughout both lungs were obtained in only 11 (50%) subjects. No significant correlations were found between regional particle deposition and pulmonary function measurements. The effects of gravity-related lung pressure gradients and ventilation-related particle residence time on the deposition of DTPA may limit its usefulness when quantitative information is required to evaluate subtle changes in ventilation in nonembolic pulmonary patients and for basic studies of ventilation and perfusion.