Key Dates

Related Announcements

• July 3, 2024- PHS 2024-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) See NOFO PA-24-245.
• July 3, 2024- PHS 2024-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed) See NOFO PA-24-247.
• March 5, 2021- NIDCR Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required) See NOFO PAR-21-160.
• May 7, 2020- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed) See NOFO PA-20-195.
• May 5, 2020 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed). See NOFO PA-20-185.

Issued by

National Institute of Dental and Craniofacial Research (NIDCR)

Purpose

This Notice of Special Interest (NOSI) is to encourage research projects to enhance accuracy, detection, diagnosis, and personalized treatment of oral lesions and inflammatory processes using advanced imaging technologies. By integrating cutting-edge imaging modalities into clinical workflows, optimizing lesion detection methods, and refining single-cell analysis, this NOSI seeks to bridge existing gaps in precision imaging for oral diseases. The long-term goal is to establish standardized quantitative imaging metrics, integrate imaging into clinical trials, and combine imaging data with multi-omics information for comprehensive profiling of oral lesions. Through collaborative research efforts, this NOSI strives to accelerate the translation of breakthrough discoveries in imaging into clinical applications, ultimately advancing the management of acute and chronic oral health conditions and improving patient outcomes.

Background

Pathological lesions in the oral cavity and oropharynx are highly diverse. They include frictional and ulcerative lesions, bacterial and fungal infections, complications of local and systemic conditions, and malignancies. In current clinical practice, differential diagnosis is based on oral examination that includes visual inspection and palpation; however, subtle lesions can pass undetected. Although some innocuous lesions may be readily diagnosed based on their clinical presentation alone, others are not as easily differentiated. It is difficult to distinguish among benign, premalignant, and malignant lesions because many mucosal conditions have a similar appearance. For example, oral cancer may present initially as a small white or red lesion, but diagnosis is often delayed until the lesion becomes unresolved. As a result, oral cancer has one of the lowest five-year survival rates (50% or less) among the major cancer types. Furthermore, dysplasia or micro-invasive carcinoma can be difficult to detect because they can be present in clinically normal-appearing mucosa.

Successful therapeutic management of oral mucosal lesions depends on a definitive, accurate, and timely diagnosis. Despite general accessibility of the mouth during physical examination, oral lesions are often not diagnosed until late stages of disease. Histological analysis of biopsy samples is the gold standard technique for diagnosis of lesions that cannot be differentiated based on clinical appearance alone. The standard approach relies on gross microscopic assessment of atypia that may not always reflect the underlying pathology or disease condition. Histopathological analyses are often complicated by low specificity and sensitivity, in addition to high intra- and inter- observer variability due to reliance on subjective and non-quantitative measures. Results may be further complicated by the quality of the biospecimens and inconsistency in sample preparation. The use of highly subjective measures to diagnose oral lesions can be dangerous because serious conditions, such as oral manifestations and complications of uncontrolled systemic diseases and cancers, may be overlooked. The lack of effective diagnostic and quantitative methods that can replace or complement conventional histopathology has clearly limited the ability of clinicians to consistently and accurately categorize oral pathologies. As a result, treating pathological conditions of the oral cavity is often challenging. New and improved methods are required to detect and analyze early mucosal changes to optimize treatment planning and reduce morbidity and mortality.

Treating lesions in the oral cavity and oropharynx remains challenging due to the reliance on subjective clinical features and histopathological diagnosis. Existing methods, such as fluorescence and toluidine stain, lack specificity and have high false-negative rates, limiting their diagnostic value. There is a critical need for more precise and sensitive tools for early detection and diagnosis, especially considering the significant health risks associated with oral lesions, including all types of infectious, inflammatory, pre-cancerous, and cancerous lesions of the soft and hard oral tissues.

While recent advancements in imaging technologies offer promise, gaps persist in precision imaging for characterizing inflammation, pre-cancer, and cancer in oral lesions. Molecular imaging significantly adds to the understanding of disease pathogenesis and is considered the gold standard in visualizing inflammation and pre-cancerous and cancerous lesions noninvasively. The specificity of the molecular probes provides risk prediction and stratification to identify patients most likely to benefit from a targeted intervention under monitoring therapy response. However, the practical limitations of its clinical deployment restrict its use in clinical practice. Key areas for improvement include early detection through imaging biomarkers, characterization of inflammatory and infectious subtypes, personalized treatment planning, intraoperative imaging for precision surgery, monitoring treatment response, early recurrence detection, and patient stratification based on inflammation and molecular profiles.

Integration of advanced imaging techniques into clinical trials is essential for evaluating their impact on patient outcomes and accelerating the translation of breakthrough discoveries into clinical applications. Furthermore, leveraging interventional oncology and surgery procedures and artificial intelligence (AI) holds promise in optimizing treatment responses and improving procedural outcomes.

By addressing these gaps through collaborative research efforts, we can revolutionize clinical practice, enhance the management of acute and chronic oral health conditions, and ultimately improve patient outcomes.

Specific Areas of Interest

This NOSI aims to drive basic, translational, and clinical research, with a focus on enhancing accuracy and novel development in differential diagnosis, therapy, and disease monitoring in the oral cavity and oropharynx, including all types of infectious, inflammatory, pre-cancerous, and cancerous lesions of the soft and hard oral tissues. Key areas of opportunity for translational research include:

• Incorporating new imaging modalities into clinical workflows to better characterize and grade oral lesions, as well as assess disease extent and severity.
• Developing reliable techniques to detect lesions that may be missed by conventional examination procedures.
• Optimizing single-cell analysis to elucidate cellular and physiological differences within heterogeneous oral lesions.
• Creating and optimizing image-guided biopsy, surgery, and ablative therapies to enhance oral disease management.
• Designing agents targeting biological pathways to identify early disease markers, treat conditions, and monitor therapeutic responses.
• Exploring imaging-based biomarkers for early detection of inflammation and aggressive phenotypes in both cancerous and non-cancerous oral lesions.
• Utilizing imaging to differentiate inflammatory and immune cell subtypes within head and neck cancers, correlating findings with molecular and immunological data and biomarkers.
• Developing imaging strategies to tailor anti-inflammatory and immunotherapeutic treatments based on individual responses and inflammatory and immune patterns.
• Employing imaging to track dynamic changes in inflammation and tumor microenvironment during and after treatment, particularly in response to immunotherapies or targeted therapies.
• Establishing imaging protocols for early identification of inflammatory and molecular changes indicative of cancer recurrence, aiding in post-treatment surveillance.

Emphasis on the establishment of standardized quantitative imaging metrics, integration into clinical trials for assessing treatment efficacy, and the integration of imaging with multi-omics data for comprehensive inflammation profiling in both cancer and non-cancer oral lesions are highly encouraged.

Applicants are strongly encouraged to contact the Scientific/Research contacts listed in Section VII to discuss the relevance of the proposed studies before submitting the application.

Application and Submission Information

This notice applies to due dates on or after October 5, 2024, and subsequent receipt dates through September 8, 2027.

NIDCR encourages applications focused on translational research, product development, and clinical implementations of novel precision imaging approaches with potential to enhance diagnosis and treatment of oral lesions. Submit applications for this NOSI in response to one of the following notice of funding opportunity (NOFO) or the subsequent reissued equivalent through the expiration date of this notice:

• PA-20-185- NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
• PA-20-195- NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
• PAR-21-160 NIDCR Clinical Trial Planning and Implementation Cooperative Agreement (UG3/UH3 Clinical Trial Required)
• PA-24-247 PHS 2024-2 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)
• PA-24-245 PHS 2024-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) 

All instructions in the SF424 (R&R) Application Guide and the parent funding opportunity announcement must be followed, with the following additions:

• For funding consideration, applicants must include “NOT-DE-25-034” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:

Scientific/Research Contact(s)

Zhong Chen, MD, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-529-7083
Email: zhong.chen@nih.gov

Orlando Lopez, PhD
National Institute of Dental and Craniofacial Research (NIDCR)
(301) 402-4243
Email: orlando.lopez@nih.gov

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Gabriel Hidalgo, MBA
National Institute of Dental and Craniofacial Research (NIDCR)
Telephone: 301-827-4630
Email: gabriel.hidalgo@nih.gov