Integrative Biology and Infectious Diseases Branch, DER, NIDCR
The purpose of this initiative is to encourage research that uses cutting edge imaging technologies to enhance detection and diagnosis and treatment of oral diseases and conditions, thereby facilitating appropriate treatment and improving patient survival and life quality. The NIDCR solicits applications that have the potential to identify and advance highly-effective precision imaging approaches that can be combined with other tools for the diagnosis of all types of non-cancerous and cancerous lesions of the soft and hard oral tissues. The long-term goal is to pave ways for personalized health care, which promote accurate and timely diagnosis, targeted and personalized therapies, and improved treatment outcomes.
Pathological lesions in the oral cavity and oropharynx are highly diverse; they range from benign, frictional or ulcerative lesions to more serious conditions such as bacterial and fungal infections, complications from local and systemic conditions and malignancies. Ulcerative as well as white and red lesions are commonly seen in dental clinics, but they can be challenging to diagnose because of their diverse appearance and etiology. Although some innocuous lesions may be readily diagnosed based on their clinical presentation alone, others are more difficult to determine clinically and histologically. Given that various mucosal conditions have a similar appearance, more analytical and quantitative evaluation processes are needed to avoid misdiagnosis, and delayed, improper care.
Histopathology remains the gold standard diagnostic technique for the characterization and classification of oral lesions. The method relies on gross microscopic assessment of cellular and nuclear atypia through microscopy that does not always reflect the underlying pathology or disease condition. Histopathology analysis also suffers from low specificity and sensitivity, and reliance on the subjective judgement that is clinician-dependent. The lack of effective diagnostic methods to replace or to complement conventional pathology has clearly limited the ability of clinicians to reliably and consistently categorize oral pathological changes; overcoming these limitations would lead to earlier intervention, and accurate and improved clinical outcomes. Methods that can enhance early detection of mucosal changes prior to their progression to a clinical lesion state are urgently needed to optimize treatment and reduce morbidity and mortality. Recent advances in the field of precision imaging have the potential to address these unmet clinical needs.
Precision imaging refers to a collection of rapidly emerging advanced, quantitative imaging technologies and imaging analysis processes that eliminate the subjectivity of visual based image data interpretation. One example of precision imaging is radiomics, which combines sophisticated image-capture, processing, machine learning, and computational techniques to allow extraction of quantifiable physical properties from morphological images (e.g., shape, size, volume, intensity and texture). These properties can be used to help assess the severity of a condition or injury, disease status, or degree of change relative to baseline. These image-derived classifiers or biomarkers, when combined with molecular signatures and clinical data, have a potential to further enhance the precision and accuracy of diagnosis in a personalized manner.
Molecular imaging is another rapidly emerging field that provides non-invasive, real time, quantitative visual representations of fundamental biological processes in living organisms. Molecular imaging combines live image-capture and processing techniques with molecular informatics to detect activity of specific molecular pathways known to play key roles in pathophysiology, thus providing unique insights into cellular/tissue heterogeneity and disease processes. Molecular probes and contrast agents can be designed to facilitate both diagnostic and therapeutic applications. For example, many preclinical and early phase clinical trial studies have demonstrated that molecular optical imaging technology can generate highly sensitive and specific information for the accurate differentiation between normal and disease tissues, supporting its potential usefulness in identifying positive surgical margins in clinical settings to ensure accurate excision for accomplishing disease-free outcome. The specificity of the molecular probes gives them additional use in risk prediction and risk stratification, in identifying patients most likely to benefit from a targeted intervention, and in monitoring therapy response.
Gaps and Opportunities
Treating lesions of the oral cavity and oropharynx is challenging for most clinicians due to the dependence on clinical features and subjective histopathological diagnosis of the lesions. Health care providers need more precise, sensitive, and quantitative tools for the early detection and diagnosis of oral lesions that can represent a source of morbidity and a serious threat to health (e.g., oral manifestations and complications of uncontrolled diabetes mellitus, risk for oral and head and neck cancers). A few new techniques for detecting premalignant and early malignant lesions have been developed over the years to supplement the clinical examination. However, the utility of these methods is still limited due to their low specificity (e.g., fluorescence, toluidine stain) and high false-negative rate (e.g., brush biopsy for cytology). While these methods improve visibility of lesions, they suffer from poor diagnostic and prognostic value. There exists a strong need to integrate high resolution, quantitative tools to enhance the diagnostic precision of oral pathology. The emergence of new imaging technologies creates an opportunity to fill the gaps in oral diseases research, to bridge the unmet clinical needs, and to pave ways for growth and acceleration of personalized medicine. Lesions in the oral cavity and oropharynx are particularly amenable to imaging and imaging-guided interventions because of the accessibility of the oral mucosal surfaces that are frequently screened by dentists during routine visits.
Specific Areas of Research Interest This initiative encourages basic and translational research projects that focus on optimizing imaging modalities and methods to improve accuracy in differential diagnosis, therapy, and in monitoring of disease progression and treatment response of lesions in the oral cavity and oropharynx. Examples of research suitable for this initiative include, but are not limited to, the following areas involving use of precision imaging modalities and approaches:
- Integration of emerging imaging technologies into clinical workflow for more effective solutions in characterizing and grading of oral lesions, and in determining the extent and severity of disease.
- Development of robust methods to detect lesions not detectable by conventional examination procedures.
- Optimization of single cell analysis to define cellular and physiological differences within heterogenous oral lesions.
- Development and optimization of intraoperative image-guided biopsy, surgery, and ablative therapies for oral disease management.
- Development of theranostic agents that target biological pathways and processes to aid in identifying early markers for an oral disease or condition, treating the disease or condition, and monitoring therapeutic effects.
Alignment with Institute Goals and Strategic Plan
This initiative is aligned with the NIDCR Strategic Plan 2014-2019, Goal 1: Support the best science to improve dental, oral, and craniofacial health and specifically with objective 1.1 that includes “Recent advances in technology offer exciting opportunities to examine these cells and tissues, in vitro and in vivo, and to develop precise clinical tools for risk assessment, screening, prevention, diagnosis, and treatment of various oral diseases”, and Goal 2: Enable precise and personalized oral health care through research and specifically with objective 2-1 that includes “ .. uncovering new approaches for diagnosing and managing disease based on molecular signatures, rather than relying mainly on symptoms and clinical assessment”. This concept also aligns with NIDCR 2030 road map.
Individuals and Groups Whose Input was Solicited for This Initiative
Relevant information was gathered from the NCI-NIDCR co-sponsored Advancement of Head and Neck Cancer Detection Research (AHEAD) workshop held on April 22-23, 2017. The workshop agenda included a session that reviewed topics on the technology development for early detection of Head and Neck Squamous Cell Carcinoma, which led to discussion of what additional tools were needed to improve detection and differential diagnostic precision. Public comments specific for this concept were solicited on NIDCR website from August 4-September 5, 2017.
A portfolio analysis of awarded NIDCR grants for the past ten years found fourteen unique grans focused on imaging research in a variety of diseases of soft and hard oral tissues, ranging from basic biological mechanisms to translational studies involving drug delivery, photodynamic therapy, tumor margin determination. Eight of these grants were for research projects and six were for SBIR projects. This initiative has shared scientific interests with NCI (oral cancer, cancer imaging) and NIBIB (imaging). Using the same search criteria, NCI funded thirty research projects and SBIR projects, and NIBIB funded four research projects. The total number of “precision imaging of oral lesions” related projects funded by NIH is very low and considerably limited compared to imaging applications on other disease types.
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