NIH – Precision Imaging of Oral Lesions (R01, R21-Clinical Trial Not Allowed)

May 23, 2018 by School of Medicine Webmaster

The following description was taken from the R01 version of this FOA.

Diagnosing and treating lesions of the oral cavity and oropharynx are challenging due to reliance on subjective analyses of clinical features and histopathological diagnostic criteria. High resolution and quantitative tools are needed to enhance the precision of diagnostic approaches for oral pathologies to guide options for treatment. This Funding Opportunity Announcement (FOA) is to encourage research projects that develop, adapt, optimize, and validate imaging-based applications and data analysis tools to enhance oral disease detection, diagnosis, and treatment. The long-term goal is to facilitate translation of research findings into clinical practice, paving the way for personalized health care through objective measures that promote accurate and timely diagnosis, targeted therapies, and improved patient survival and quality of life.

This FOA will utilize the Research Project Grant (R01) mechanism and is suitable for projects where proof-of-principle of the proposed technology or methodology has already been established and supportive preliminary data are available.

This FOA runs in parallel with an FOA of identical scientific scope, PAR-18-788, which utilizes the Exploratory/Developmental Grant (R21) mechanism.


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.

Specific Objectives Of This FOA  

The specific scope of this Funding of Opportunity Announcement (FOA) is to address challenges of detection, diagnosis and treatment of lesions in the oral cavity and oropharynx. The National Institute of Dental and Craniofacial Research (NIDCR) recognizes the unmet need for more sensitive and quantitative tools for management of oral diseases. A few simple techniques for detecting precancerous and early malignant lesions have been developed over the years to supplement oral 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).   Considerable progress has been made in precision imaging technologies and methods for the acquisition of anatomical, functional, and molecular imaging data.  Improvements in tools for data analyses, display methods, and reporting structures would enable quantification of physiological structures and biological functions for monitoring dynamic biological processes at the cellular and subcellular scales. This FOA will support research that applies these technological advances to improve diagnosis of oral diseases and lead to more precise, personalized treatment.

This FOA invites applications that propose to adapt, optimize, and validate existing imaging systems or develop new image-based methodologies and analytic tools capable of improving early detection, diagnosis, and targeted treatment of oral diseases and conditions.  Studies may include single or multi-modality in vivo imaging and spectroscopy systems, image-guided intervention and drug delivery systems, image analysis, and molecular imaging probe design and development.   This FOA will support preclinical studies, and studies that use clinical samples or perform secondary analysis of imaging and metadata from existing clinical trials as needed to validate the imaging tools and methods under investigation.

Examples of research projects may include, but are not limited to the following:

  • Leverage advances in image capture, processing, contrast, resolution, and molecular identity to help locate lesions that are not detectable by currently used approaches, to enhance early detection of mucosal changes prior to their progression to a clinical lesion state, and to characterize and grade oral lesions and conditions in determining the extent and severity of disease.
  • Develop image-derived classifiers or biomarkers capable of reflecting structural and morphological changes within tissues for screening and monitoring oral lesions, and for tracking lesion progression over time, mapping spatial heterogeneity within the lesion, and independent evaluation of different lesions within an individual.
  • Combine imaging methods for visualization of oral lesions with molecular biomarkers to improve precision and accuracy of diagnosis and treatment.
  • Develop multimodal, multiparameter, and multiplex imaging technologies that will lead to new ways of studying oral biology and diseases.
  • Optimize single cell imaging to define cellular/tissue heterogeneity in oral lesions at initial appearance and during disease progression.
  • Develop imaging methodologies to assess dynamic or longitudinal evaluation of molecular characteristics and cell populations of oral cancer and its microenvironment.
  • Develop intraoperative image-guided biopsy, surgery, and ablative therapies to optimize disease management.
  • Develop theranostic imaging agents that target biological pathways and processes to aid in identifying early markers for oral lesions and conditions integrated with drug delivery and other therapeutic interventions as well as monitoring therapeutic responses and complications.

Projects that are not appropriate to NIDCR for this FOA include:

  • Develop reagents (e.g., probes, contrast agents) without using them in an imaging application to address a defined oral pathological problem.
  • Focus on hardware development, computer software use or training, data generation, data mining, data storage, or computational modeling and simulation without applying them in an imaging-based application to address a defined oral pathological problem.
  • Biomarker discovery.

Scientific interests of partnering NIH Institutes, the National Cancer Institute (NCI) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB), are delineated below:

The National Cancer Institute (NCI): NCI is interested in research projects using in vitro and in vivo imaging for the study of oral lesions in relation to early detection, prediction, diagnosis, prognosis, and image-guided treatment of cancers of the oral cavity, as well as evaluation of cancer aggressiveness and response to treatment.

The National Institute of Biomedical Imaging and Bioengineering (NIBIB):   The mission of NIBIB is to improve health by leading the development and accelerating the application of biomedical imaging and bioengineering tools, methods, devices, and technologies for the prevention, detection, quantification, treatment, and monitoring of disease.  The technology may focus on translation of methods, devices, and tools for pre-clinical research, pediatrics, and retrospective data analysis.

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.

Deadlines:  standard dates and standard AIDS dates apply (letters of intent due 30 days prior to the deadline)


Filed Under: Funding Opportunities