PROJECT SUMMARY Periodontitis and oral disease are widespread with major and negative impacts on quality of life. Radiography is the standard of care in imaging but is limited to assessment of hard tissue. In the last three years, we have shown that ultrasound imaging offers significant advantages to oral health including non-invasive and real- time assessment of the periodontal probing depths, cementoenamel junction, gingival thickness, gingival perfusion/hypoxia, and clinical attachment loss. However, further clinical work in this field is limited by the large size of the ultrasound transducers—they are simply too large to access the posterior teeth. While smaller transducers exist, they cannot operate at the high frequency (>40 MHz) needed to image the small feature sizes involved in oral health. Therefore, we have established a three-way academic-industrial partnership to refine and finalize these devices for oral health. Dr. Jokerst at UCSD serves as PI and pioneered the use of photoacoustic imaging in oral health. VisualSonics Corp. is our industrial partner—Dr. Jokerst’s preliminary data was collected on VisualSonics equipment, and this company has a 20-year track record in developing high-frequency transducers including recent 510k-approved systems for human use. The clinical partner is Dr. Casey Chen who is Chair of Periodontology at USC and who will validate the system with human subjects. Aim 1 of the work will build and validate a small hockey stick-style transducer. While this design is already common, hockey stick transducers above 20 MHz are not available. Aim 2 will integrate diode lasers into the system for photoacoustic imaging to complement ultrasound. Aim 3 will develop image-processing algorithms to automatically export metrics of oral health such as clinical attachment loss and probing depth. Such automated image-processing is critical to broad clinical acceptance. Aim 4 will validate this device in healthy and diseased human subjects with comparisons to clinical gold standards. The significance of this work is based on the widespread prevalence of periodontal disease and the remarkable new insight that acoustic imaging offers in diagnosis and treatment planning. The innovative outcomes include non-invasive charting, direct measurements of the cementoenamel junction, noninvasive biotyping, and 3D maps of inflammation near implants. The work is feasible because of the track record of all three partners as well as their history of collaboration. This is a good investment for NIH because there is no miniaturized and high-frequency (>40 MHz) ultrasound transducer available despite the dramatic improvement in spatial resolution that high frequency offers. The proposal offers deliverables at all ranges of risk and the ultrasound transducer is highly likely to succeed with implications well beyond oral health: Applications in endoscopy, head and neck diseases, as well as transrectal/transvaginal imaging are obvious.

PROJECT NARRATIVE Dental health is critical to quality of life, but the tools that dentists and periodontists use to inspect the mouth have major limitations related to studying the gingiva. This work will build an ultrasound-based device to non- invasively map and measure periodontal disease easily, earlier, and more accurately. The imaging approach will evaluate the entire pocket and be less variable than the existing method—this will improve quality of life.