. Noninvasive real-time measurement of nasal mucociliary clearance in mice by pinhole gamma scintigraphy. J Appl Physiol 108: 189 -196, 2010. First published October 1, 2009 doi:10.1152/japplphysiol.00669.2009 is the key defense mechanism in the upper airways, as the removal of debris-laden mucus in the sinuses completely depends on MCC. So far, how the nasal MCC is regulated remains unknown. Recently, mice deficient in genes encoding the components of MCC apparatus have been generated, which will allow investigators to conduct more in-depth nasal MCC studies. However, the methodology necessary to comprehensively evaluate the nasal MCC in this species is not well established. We therefore developed a novel method to measure nasal MCC in live mice using pinhole gamma camera. Insoluble radiolabeled particles were delivered into the noses of lightly anesthetized mice. The nasal clearance of these particles was measured continuously in a real-time manner. The effect of three different anestheticsavertin, pentobarbital, and isoflurane-on nasal MCC was also determined. In mice anesthetized by 1.1% isoflurane, radiolabeled particles were immediately moved into the oropharynx, which was significantly accelerated by the treatment of hypertonic but not isotonic saline. According to the clearance rate, the mouse nasal MCC presented two distinct phases: a rapid phase and a slow phase. In addition, we found that isoflurane had a very small inhibitory effect on nasal MCC vs. both avertin and pentobarbital. This was further supported by its dose response. Collectively, we have developed a noninvasive method to monitor the real-time nasal MCC in live mice under physiological conditions. It provides more comprehensive evaluation on nasal MCC rather than assessing a single component of the MCC apparatus in isolation.anesthesia; isoflurane; avertin; pentobarbital; hypertonic saline MUCOCILIARY CLEARANCE (MCC) is an important innate defense mechanism by which both upper and lower airways cleanse their surface of inhaled pollutants, allergens, pathogens, and mucus secreted by goblet cells and submucosal glands. This protective mechanism is especially important in the upper airways and sinuses, as the removal of debris-laden mucus in the sinuses completely depends on MCC, whereas in the lower airways MCC can be compensated for by other mechanisms such as coughing (43). This hypothesis is further supported by the observations that mice with primary ciliary dyskinesia (PCD) only exhibit inflammation in the nose and sinuses but not in the lower airways and lungs; and that sinonasal symptoms usually emerge in the early stage of PCD patients (6,26,28,32,45). These observations have led to the theory that impaired MCC in the nose and sinuses is the central pathophysiological process in the pathogenesis of chronic rhinosinusitis (CRS), a disease that currently affects more than 12% of Americans more than 18 years old (35). The major purpose of diverse therapeutic strategies for CRS patients is to improve and restore their sinonasal MCC fun...