2007 — 2009 |
Zhao, Kai |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Nasal Airflow and Odorant Transport: a Prerequisite For Normal Olfaction @ Monell Chemical Senses Center
[unreadable] DESCRIPTION (provided by applicant): Mechanical obstruction of air/odorant flow to olfactory receptor sites may be a primary cause of olfactory loss in nasal-sinus disease patients. Unfortunately, quantifying the functional impact of various nasal obstruction and the subsequent surgical outcomes using acoustic rhinometry, rhinomanometry or CT scans is inadequate. Studies have shown a poor correlation between these existing objective measurements with patients' subjective symptoms. Recently developed computational fluid dynamic (CFD) modeling techniques have shown promise for quantifying the location-dependent, obstruction-induced changes in nasal airflow pattern and odorant mucosal deposition and have the potential to characterize their functional impact on patients' olfactory function. The goal of this application is to establish a baseline in nasal airflow pattern and odorant delivery rate among healthy subjects, from which the putative conductive mechanisms of olfactory loss among clinical patients can be verified in future. In the future, such modeling techniques may provide quantitative evaluation of surgical procedures and an important pre-operative guide to optimize airflow and odorant delivery in human nose. [unreadable] [unreadable] [unreadable]
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2015 — 2018 |
Zhao, Kai |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Objective Evaluation of Conductive Olfactory Losses & Nasal Obstruction Symptoms
Project Summary Nasal sinus disease is one of the most common medical conditions in the US, affecting an estimated 13% of adults, or more than 29 million people. Nasal obstruction and smell loss are two of the major symptoms of the disease; however, the field currently lacks a clear, objective understanding to the mechanisms causing these symptoms, which limits effective disease management. For example, patients' complaints of nasal obstruction correlate poorly or inconsistently with objective measurements of actual physical obstruction. Olfactory loss has been widely believed to be induced in part by airflow blockage; however, no tool has been able to quantify or predict such a mechanism. We propose to develop and validate a novel objective diagnostic tool for nasal obstructive symptoms, based on two hypotheses (a) that perception of nasal obstruction (lack of patency) is due to lack of nasal cooling caused by physical nasal conditions, and/or inadequate sensory feedback, and (b) that insufficient conduction of air/odorant flow specifically to the olfactory region contributes to olfactory losses. To test these hypotheses and pursue a clinical tool, we will conduct a study and focus on three aims. In Aim 1, we will use individualized computational fluid dynamics (CFD) nasal models based on patient CT scans to assess insufficient mucosal cooling due to existing airway abnormalities, and determine if this correlates with patient symptom ratings. We will further perturb patients' nasal airway temporarily with a nasal dilator and decongestant and test whether our approach can predict perceptual symptom changes. In Aim 2, we will broadly assess the trigeminal cool sensitivity of patients with the symptom of nasal obstruction, and determine whether abnormal trigeminal cool sensitivity (including the TRPM8 pathway) contributes to symptoms. TRPM8 is a major component of the cool afferent pathway that is also activated chemically, which offers a unique dual investigatory tool and potentially broadens our understanding of chemosensory functions in nasal inflammatory disease. In Aim 3, we will specifically target nasal polyp patients with olfactory losses, track their treatment progress, and determine if the CFD-predicted air transport and odorant sorption rate to the olfactory region correlate with olfactory function losses and recovery. The outcomes from this research may validate how to combine one or several measurements into an effective clinical tool to differentiate the causal factors leading to a patient's conductive symptoms, to potentially identify the site that most affects the symptom, and to guide move effective treatment or surgery in the future.
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2019 — 2020 |
Zhao, Kai |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Endoscopic Nasal Sinus Surgery Simulator to Optimize Treatment Outcome
Project Summary Millions of endoscopic nasal sinus surgeries are performed annually worldwide, yet the outcomes are often variable. One reason is that predicting functional outcomes (e.g. nasal airflow) based solely on CT or endoscopy can be difficult. The lack of an objective planning system results in ineffective disease management. For this proposal, a unique multidisciplinary team of clinicians, computer scientists, and engineers was assembled to develop a virtual endoscopic sinus surgery simulator that would simulate patient anatomy, reveal flow obstructions, and ultimately facilitate optimization of the outcome of surgical approaches for treatment of nasal obstruction and conductive olfactory loss. Using virtual reality, the surgeon can remove obstructive tissue virtually through a haptic (tactile and kinesthetic) feedback device. After each virtual surgery, changes in nasal airflow can be computed and displayed and the process reiterated until an optimal result is reached. A trial using this approach was performed on four patients as a proof of concept, and a normative range of air/odor flow based on 22 healthy controls was established. We will continue to improve the overall fidelity of our system (Aim 1) by incorporating feedback from clinicians and iterative innovation employing recent advances in computer science (image processing, volume visualization, haptic modeling, interface design). We will also perform non-interventional trials on 20 patients and focus on nasal obstruction related olfactory loss (Aim 2) and test the hypothesis that the virtual sinus surgery simulator can improve treatment outcomes to conductive olfactory loss. While this proposal is limited to the specific symptom of obstruction-related olfactory loss, but in the future the tool can be expanded to improve outcomes for more generalized nasal obstruction symptoms. Ultimately, developing and validating such a virtual surgical planning system will prove invaluable for future surgical treatment of nasal obstruction and has the potential to directly improve clinical practice and offer personalized medicine.
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