Grant: Collaborative Health Research Projects

Research Objectives: 1) To longitudinally establish differentiating spectral features that distinguish between progressing and stable chronic periodontitis lesions (sensitivity, specificity and robustness) using a recently developed near infrared (NIR) intraoral probe (supported by a previous CHRP grant). 2) To establish and characterize an animal model (rabbit) for periodontitis that simulates the major features of the disease in humans in order to elucidate relationships between the spectroscopic measurements and histopathological alterations at different stages of the disease; and 3) To evaluate the potential of high frequency ultrasound as a direct morphological probe for the in vivo measurement and imaging of periodontal pocket formation. Scientific Approach: 1) Human subjects: A total of 500 subjects will be recruited from those with chronic periodontitis who are undergoing maintenance treatment at three independent locations (Canada, USA and China). Annual clinical assessment including bleeding on probing (BOP), probing depths (PD), clinical attachment loss (CAL), and alveolar bone loss will be measured at one or more diseased sites. In vivo NIR spectra will be collected using a custom built intraoral NIRS system and in vitro Mid IR spectra of gingival crevicular fluid (GCF) will be collected from diseased and control sites. In addition, a handheld 50MHz acoustical microscope will be employed to examine the areas of soft tissue detachment and pocket depth. 2) Rabbit model: Experimental periodontitis will be produced in New Zealand White rabbits (n=10) by ligature placement. Histological parameters including HE, TRAP and MMPs of the experimental periodontitis will be determined. Spectroscopic, ultrasonic, and clinical (POB, PD, CAL) measurements will be carried out on sedated rabbits simultaneously. Innovativeness and significance: Periodontitis is an inflammatory disease initiated by bacterial accumulation that leads to loss of tooth-supporting tissues and resorption of alveolar bone. However, current diagnostic procedures do not reliably identify susceptible individuals nor distinguish between disease-active and disease inactive sites. Recently, we have demonstrated that optical spectroscopy (supported by previous CHRP grant) can be used to measure regional tissue hemodynamics and edema - a potential new novel tool for the diagnosis of periodontitis, as we originally hypothesized (Liu et al, J. Periodont. Res. 2008). The innovativeness of the current proposal lies in capitalizing on the breakthroughs achieved in our previous CHRP grant. The current proposal will perform the next set of studies required to bridge laboratory findings to clinical implementation. We plan to execute a "3 M" strategy- Multicenter (Canada, USA, China), Multimodel (Human and animal), and Multimodality (Near-infrared spectroscopy, Mid-infrared spectroscopy and Ultrasonic imaging). The success of this anticipated CHRP grant will provide essential pre-clinical data (a) longitudinal assessment of disease progression by infrared modalities; (b) associations of spectroscopic results to the histopathological alterations associated with periodontitis (animal model); and (c) the development of a further innovative imaging tool (ultrasonic microprobing) that will permit comparisons of in vivo digital images of the periodontal soft tissue with infrared-derived inflammatory indices. The development, regulatory approval and marketing of a non-invasive diagnostic suite will provide a much-needed screening and diagnostic and prognostic tool for inflammatory periodontal diseases that will represent a major breakthrough for the field of dental medicine in Canada and beyond.