Date: January 24, 2017
Place: Conference Room 10
National Institutes of Health
The 214th meeting of the National Advisory Dental and Craniofacial Research Council (NADCRC) was convened on January 24, 2017, at 8:33 a.m., in Building 31, Conference Room 10, National Institutes of Health (NIH), Bethesda, Maryland. The meeting was open to the public from 8:33 a.m. to 12:04 p.m.; it was followed by the closed session for Council business and consideration of grant applications from 1:45 p.m. until adjournment at 2:13 p.m. Dr. Martha Somerman presided as Chair.
- Dr. Patricia E. Arola (ex officio)
- Dr. Shenda M. Baker
- Dr. Terence S. Batliner
- Dr. Yang Chai
- Dr. Richard Peters Darveau
- Dr. Nisha J. D’Silva
- Ms. Tracy Hart
- Dr. Daniel Malamud (via telephone)
- Dr. Anne Louise Oaklander
- Dr. Sanjay Shete
- Dr. Anne C. R. Tanner
- Dr. Jane A. Weintraub
- Dr. Daniel W. McNeil
Members of the Public
- Dr. Marcelo W. B. Araujo, Vice President, Science Institute, American Dental Association (ADA), Washington, D.C.
- Dr. Robert J. Burns, Manager, Legislative and Regulatory Policy, ADA, Washington, D.C.
- Dr. Christopher Fox, Executive Director, International Association for Dental Research (IADR) and American Association for Dental Research (AADR), Alexandria, VA
- Dr. John V. Frangioni, Chief Executive Officer, Curadel, LLC, Marlborough, Massachusetts, and Professor Emeritus, Harvard Medical School, Cambridge, MA
- Dr. Benson Hall, Founder and Member, Board of Directors, Atlas Volumetrics, Inc., Richmond, VA
- Dr. Linda Kaste, AADR Scholar in Residence, and Associate Professor of Pediatric Dentistry, University of Illinois at Chicago College of Dentistry, Chicago, IL
- Mr. B. Timothy Leeth, Senior Director for Federal Relations, American Dental Education Association (ADEA) Policy Center - Advocacy and Governmental Relations, ADEA, Washington, D.C.
- Mrs. Carolyn Mullen, Director of Government Affairs, IADR and AADR, Alexandria, VA
- Dr. Jeffrey Stewart, Senior Director, Institutional Innovation and Development, ADEA Learning Center, ADEA, Washington, D.C.
- Dr. James J. Xia, Director, Surgical Planning Laboratory, Department of Oral and Maxillofacial Surgery, Houston Methodist Research Institute, and Professor, Institute for Academic Medicine, Houston Medical Hospital, Houston, TX; and Professor of Oral and Maxillofacial Surgery, Weill Medical College of Cornell University, New York, NY
Federal Employees Present
National Institute of Dental and Craniofacial Research
- Dr. Martha J. Somerman, Director
- Dr. Alicia Dombroski, Executive Secretary, and Director, Division of Extramural Activities (DEA)
- Dr. Lillian Shum, Director, Division of Extramural Research (DER)
- Dr. Robert Angerer, Scientific Director, Division of Intramural Research (DIR)
- Dr. John W. Kusiak, Office of the Director (OD), Acting Deputy Director
- Dr. Margo Adesanya, OD, Office of Science Policy and Analysis (OSPA)
- Ms. Tamera Addison, OD, Office of Administrative Management (OAM)
- Dr. Jane Atkinson, DER, Center for Clinical Research (CCR)
- Dr. Nisan Bhattacharya, DEA, Scientific Review Branch (SRB)
- Ms. Karina Boehm, OD, Office of Communications and Health Education (OCHE)
- Dr. Latarsha Juanita Carithers, DEA, SRB
- Dr. Preethi Chander, DER, Integrative Biology and Infectious Diseases Branch (IBIDB)
- Dr. Dave Clark, DER, Behavioral and Social Sciences Research Branch (BSSRB)
- Ms. Michelle Cortes, DER IBIDB
- Ms. Mary A. Cutting, DER, CCR
- Ms. Mary Daum, OD, Health Information and Public Liaison Branch (HIPLB)
- Mr. Bret Dean, OAM, Financial Management Branch (FMB)
- Dr. Olga Epifano, DEA
- Dr. Catherine Evans, OD, OCHE
- Dr. Dena Fischer, DER, CCR
- Dr. Leslie Frieden, DEA, Research Training and Career Development Branch (RTCDB)
- Dr. Crina Frincu, DEA, SRB
- Dr. Gallya Gannot, DER, CCR
- Dr. Nicole Garcia-Quijano, OCHE, HIPLB
- Mr. Joel Guzman, DER, Translational Genomics Research Branch (TGRB)
- Dr. Sue Hamann, OD, OSPA
- Ms. Jeannine Helm, DER
- Mr. Gabriel Hidalgo, DEA, Grants Management Branch (GMB)
- Dr. Jonathan Horsford, OD, OSPA
- Dr. Laura Hsu, DER, CCR
- Ms. Nakita Jan Kanu, OD
- Dr. Wendy Knosp, OD, OSPA
- Dr. Denise K. Liberton, DIR, Craniofacial Anomalies and Regeneration Section
- Ms. Carol Loose, OAM, FMB
- Dr. Orlando Lopez, DER, IBIDB
- Ms. Susan Lowenthal, DEA, GMB
- Dr. Nadya Lumelsky, DER, IBIDB
- Dr. R. Dwayne Lunsford, DER, IBIDB
- Ms. Jayne Lura-Brown, DER
- Ms. Yasamin Moghadam, DER, CCR
- Dr. Marilyn Moore-Hoon, DEA, SRB
- Mr. Paul Newgen, DEA, GMB
- Ms. Anna Nicholson, OD, Office of Clinical Trials Operations and Management (OCTOM)
- Mr. Michael David North, OAM
- Dr. Morgan O’Hayre, OD
- Ms. Debbie Pettit, DEA, GMB
- Ms. Ann Poritzky, OCHE, Science Communication and Digital Outreach Branch (SCDOB)
- Mr. John Prue, OD, Office of Information Technology (OIT)
- Mr. Mo Qiao, OD
- Mr. Ben Rassuli, OD, OIT
- Dr. Melissa Riddle, DER, BSSRB
- Ms. Delores Robinson, DEA
- Ms. Diana Rutberg, DEA, GMB
- Dr. Steven Scholnick, DER, TGRB
- Dr. Yasaman Shirazi, DEA, SRB
- Dr. Kathryn Stein, DER, TGRB
- Ms. Kathleen Stephan, OD
- Mr. Christopher Suggs, DER
- Mr. Larry Sutton, OD, OAM
- Mr. Joseph Tiano, OD, OSPA
- Dr. Yolanda Vallejo-Estrada, DER, IBIDB
- Dr. Jessica Walrath, OD, OSPA
- Dr. Darien Weatherspoon, DER, CCR
- Dr. Gary Zhang, DEA, SRB
- Dr. Lois K. Cohen, Consultant
Other Federal Employees
- Dr. Tom Hart, Senior Director, ADA Foundation, Dr. Anthony Volpe Research Center, National Institute of Standards and Technology (NIST), U.S. Department of Commerce (DOC), Gaithersburg, MD
I. WELCOME AND INTRODUCTIONS
Dr. Martha Somerman, Director, NIDCR, called the 214th meeting of the Council to order. She welcomed everyone, including Council members, guests, and participants attending via the NIH videocast (http://videocast.nih.gov). She encouraged the Council members to peruse the latest New Investigator Profiles booklet, which was distributed to them. She then invited all guests to introduce themselves.
Dr. Alicia Dombroski, Executive Secretary, and Director, Division of Extramural Activities (DEA), welcomed the participants and asked staff to introduce new or reassigned NIDCR personnel. Ms. Kathleen Stephan, Executor Officer, Office of the Director, introduced two staff members in the Office of Administrative Management (OAM), Ms. Tamera Addison and Mr. Michael North. Dr. Yasaman Shirazi, chief of the Scientific Review Branch, DEA, introduced Dr. Nisan Bhattacharya, who recently returned to the NIDCR as scientific review officer. Dr. Nadya Lumelsky, chief of the Integrative Biology and Infectious Diseases Branch (IBIDB) in the Division of Extramural Research (DER), introduced Dr. Preethi Chander, who was recently appointed director of IBIDB’s Salivary Biology and Immunology Program, and Ms. Michelle Cortes, a specialist in DER.
Ms. Karina Boehm, director of the Office of Communications and Health Education (OCHE), introduced Dr. Catherine Evans, a science writer in OCHE. Dr. Morgan O’Hayre, Special Assistant to the Director and Deputy Director, NIDCR, introduced Ms. Nakita Kanu, an NIDCR contractor for outreach, who will focus on the initiative, “NIDCR: A Vision for 2030.” Dr. Jane Atkinson, director of the Center for Clinical Research (CCR), DER, introduced Ms. Yasamin Moghadam, a health specialist in CCR, and Dr. Darien Weatherspoon, the new director of the Oral Health Disparities Program, CCR. Dr. Jonathan Horsford, acting director of the Office of Science Policy and Analysis (OSPA), introduced two OSPA health science policy analysts, Mr. Joseph Tiano and Dr. Jessica Walrath.
II. FUTURE MEETING DATES
- May 23, 2017
- September 15, 2017
- January 31, 2018
- May 25, 2018
- September 13, 2018
III. APPROVAL OF MINUTES FROM PREVIOUS MEETING
Dr. Alicia Dombroski invited the Council to consider and approve the minutes of the September 20, 2016, Council meeting. The Council unanimously approved the minutes.
IV. ANNUAL REVIEW OF COUNCIL OPERATING PROCEDURES
Dr. Dombroski noted that, each January, the NIDCR and the Council review the Council’s operating procedures to recommend updates or changes. She said the NIDCR was recommending no changes this year, and she invited the Council to comment. The Council recommended no changes and unanimously approved the existing operating procedures.
V. REPORT OF THE DIRECTOR, NIDCR
Dr. Somerman reported on the budget for Fiscal Year (FY) 2016 and presented other updates. Her written Director’s Report to the Council: January 2017 was provided to the Council members and is available on the NIDCR website.
NIDCR Budget, Portfolio, and Funding Trends
Dr. Somerman reported that the NIDCR is currently operating under a Continuing Resolution until April 2017. In FY 2016, the NIDCR budget totaled $412.7 million, which is a 3.8 percent increase over the FY 2015 budget. Approximately 78 percent of the budget ($320.6 million) supported extramural research; approximately 16 percent ($65.8 million) supported intramural research; and approximately 6 percent ($26.1 million) was for research management and support. The bulk of the budget went to research project grants (RPGs). Dr. Somerman noted that the NIDCR received approximately 850 extramural research grant applications and funded 172 awards, for a success rate of approximately 20 percent. The NIDCR supported a total of 673 extramural research grants, which comprised 607 RPGs [of which 26 were Small Business Innovation Research (SBIR) and Small Business Technology Transfer (STTR) grants], 3 research centers, 42 research career awards, and 21 other research-related awards. In addition, the extramural research portfolio included funding for 230 research training awards and 18 research contracts.
Dr. Somerman emphasized that RPGs are the NIDCR “lifeline” and, as in previous years, accounted for approximately 64 percent of the total budget and 83 percent of the extramural budget. Also similar to previous years were the percentages allocated to investigator-initiated research (R01s) (more than 60 percent) and to cooperative agreements (U awards), high-priority short-term awards (R56s), research education grants (R25s), and conference awards (R13s). Dr. Somerman reported that the NIDCR success rate of approximately 20 percent parallels and is slightly higher than the average success rate for the NIH. She noted also that the success rate of applications reflects the number of applications received, and she encouraged more new investigators to apply for the NIDCR Small Grant for New Investigators (R03).
Funding Opportunity Announcements (FOAs)
In FY 2016, the NIDCR awarded a number of research grants received in response to Requests for Applications (RFAs). Most of these were R01 awards, which included six grants for research to eliminate HIV and related opportunistic infections, four grants for development of an anti-HIV vaccine, and one grant to study plasticity of the oral immune system in chronic HIV infection. Additional awards included one Exploratory Development Grant (R21) and six R01 grants to elucidate the effects of e-cigarette aerosol mixtures, four grants to develop novel or enhanced dental restorative materials for class V lesions, and two grants to better understand the pharmacogenomics of orofacial pain management. Dr. Somerman noted, in particular, that the NIDCR was pleased to be able to fund two NIDCR awards for Sustaining Outstanding Achievement in Research (SOAR) (R35).
Dr. Somerman reported that applications received in response to RFAs for FY 2017 funding are still in the review‒award process. She noted that the NIDCR is looking forward to the funding of research on biosensors in the oral cavity; the next phase of establishing the Resource Centers for Dental, Oral, and Craniofacial Tissue Regeneration Consortium; additional SOAR awards; and continued research on anti-HIV vaccines and on plasticity of the oral immune system in chronic HIV infection. The NIDCR also hopes to award administrative supplements for career development in clinical and translational research on dental, oral, and craniofacial diseases and disorders. The supplements would be supported in partnership with the NIH’s National Center for Advancing Translational Sciences (NCATS), which sponsors the Clinical and Translational Science Award (CTSA) Program.
Program Announcements (PAs) that the NIDCR will issue in FY 2017 will encourage applications for R01s and R21s in a number of areas. They include biology of temporomandibular joint disorders; genetics and genomics, gender differences, and immune system plasticity in dental, oral, and craniofacial diseases and disorders; Bioengineering Research Grants (BRGs); behavioral and social measures of dental, oral, and craniofacial health; pain management; and tailoring of dental treatment for individuals with systemic diseases compromising oral health. In FY 2018, the NIDCR plans to both fund implementation science research to improve dental, oral, and craniofacial health and reissue the RFA for SOAR awards.
Dr. Somerman noted that the Council recently approved five concepts and the NIDCR is moving forward to develop FOAs in these areas. Applications will be sought for a dental specialty/Ph.D. program; research on neuroskeletal biology of the craniofacial complex; two HIV initiatives (oral HIV pathogenesis, mucosal immunity, and prophylactic vaccine modulation by the oral microbiome, and oral prophylactic HIV vaccine-induced humoral immunity and HIV-specific B cell ontogeny); and research targeting head and neck cancers for immunotherapy.
Appropriations, Legislation, Transition
Dr. Somerman stated that the NIDCR’s purchasing power vis-à-vis its appropriation rose in FY 2016, but still has not yet caught up with inflation and remains below the FY 2003 purchasing power. She reported that the Congress passed the 21st Century Cures Act, which authorizes $4.8 billion for the NIH over the next 10 years. Funds will be appropriated each year and have been appropriated for FY 2017 under the Continuing Resolution, with specific support mandated for the Cancer Moonshot, BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, Precision Medicine Initiative, and regenerative medicine. Dr. Somerman noted that the Act includes policy changes for the NIH. Key points of interest to the NIH are measures to reduce administrative burden; support for research innovation and new investigators [e.g., Eureka (Exceptional Unconventional Research Enabling Knowledge Acceleration) prize competitions, a Next Generation Researchers Initiative, and an increased loan repayment cap]; and provisions for privacy, data access, and inclusion (e.g., authorization for the NIH Director to require funding recipients to share data). Dr. Somerman referred the Council to a recently published perspective, entitled “The 21st Century Cures Act – The View from the NIH,” coauthored by Dr. Kathy L. Hudson and Dr. Francis Collins [New England Journal of Medicine 376 (2):111‒113, January 12, 2017].
Regarding the transition between Administrations, Dr. Somerman noted that Representative Tom Price was nominated as the new Secretary, Department of Health and Human Services [Dr. Price was subsequently confirmed on February 10] and that Dr. Collins is held over currently as Director, NIH. She named four dentists now serving in the 115th Congress [Dr. Mike Simpson (R-Idaho), Dr. Brian Babin (R-Texas), Dr. Paul Gosar (R-Arizona), and, newly elected, Dr. Drew Ferguson (R-Georgia)] and noted changes in the membership of congressional authorizing and appropriations committees whose purview includes the NIH.
DIR Reorganization. Dr. Somerman presented a proposed organizational change for the DIR. Formerly consisting of 25 investigators in five laboratories and branches, the new DIR would consist of 25 investigators in one branch called Basic, Translational, and Clinical Research. The goals are to eliminate administrative “stove piping” and promote interactions and collaborations; to retain areas of emphasis while allowing them to evolve; and to promote more participatory governance with input from all investigators. The proposed reorganization will be posted for public comment on the NIDCR website on January 30.
Clinical Trials. Dr. Somerman outlined NIH-wide efforts to enhance rigor and transparency in clinical trials, from the receipt of applications to peer review, implementation and conduct of trials, and reporting and dissemination of data. Dr. Somerman noted that the Policy on Good Clinical Practice (GCP) Training became effective on January 1; the policy on Clinical Trials Registration and Summary Results Submission became effective on January 18; and the Clinical Trial Protocol Template is to be released in early 2017. Information on these and other efforts under way is available at the NIH Office of Extramural Research website, https://nexus.od.nih.gov/all/2016/09/16/clinical-trials-stewardship-and-transparency/.
Dr. Somerman encouraged Council members to also contact Dr. Anna Nicholson, director of the NIDCR Office of Clinical Trials Operations and Management (OCTOM), at firstname.lastname@example.org. or 301-594-1852.
Big Data. Dr. Somerman reported that the NIH Big Data to Knowledge (BD2K) initiative will be transferred to the National Library of Medicine (NLM). Dr. Phil Bourne, Associate Director for Data Science, NIH, who led the effort, is heading to the University of Virginia, where he will be the Stephenson Chair of Data Science, director of the Data Science Institute, and professor, Department of Biomedical Engineering. Dr. Patti Brennan, director of NLM, will become NIH’s Acting Associate Director for Data Science. Dr. Jim Anderson, director of the Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI), in the Office of the Director, NIH, will assume responsibilities for the Common Fund. Dr. Somerman noted that BD2K offers many opportunities for research that now, in the second phase, includes several NIDCR grants. She encouraged the Council members to inform their faculty colleagues and students about the BD2K opportunities, which include research training.
Research and Training at Dental Institutions. Dr. Somerman encouraged the Council members to peruse and relay the many opportunities for research and training supported by the NIDCR in partnership with the American Association for Dental Research (AADR). She thanked Dr. Christopher Fox, director of the AADR and the International Association for Dental Research (IADR), for the AADR’s commitment. Dr. Somerman noted that about 50 percent of dental institutions receive NIDCR funds for research and the NIDCR maintains strong support for faculty development and student training. The NIH’s support of dental institutions is captured in a recent article, entitled “The NIH’s Funding to U.S. Dental Institutions from 2005 to 2014,” by Drs. Chantelle Ferland, Morgan O’Hayre, Wendy Knosp, Christopher Fox, and Jonathan Horsford [Journal of Dental Research 96(1):10‒16, 2017].
NIDCR 2030: Envisioning the Future. Dr. Somerman reported that the NIDCR plans to launch its website for submission of ideas to the NIDCR 2030 initiative, using the Web-based tool Ideascale, in March. She encouraged the Council’s participation and input. Five visionary goals to achieve by 2030 are to develop three innovative research areas, tools and technologies for assessment of health and disease, and a multidisciplinary, diverse research workforce. The three proposed areas of innovative research are as follows: ensuring that oral health is integrated into the study of overall health, establishing precision health innovations and integration for all communities, and developing new autotherapy strategies (which will also be a focus of NIDCR’s 70th anniversary celebration later in 2017). Dr. Somerman said the NIDCR will convene workshops to consider and refine the unique ideas received, develop several high-risk, high-reward initiatives, and stimulate high-quality proposals in new areas. She invited the extramural research community to “connect with us” on the NIDCR website via Twitter, LinkedIn, YouTube, and email, for science news and updates and for information on grants and funding.
In discussion, the Council noted the need to define what oral health is and to address it through prevention and to increase and sustain research at more dental institutions.
VI. CONCEPT CLEARANCE
Dr. Dombroski stated that the NIDCR is required to present the purpose, scope, and objectives of staff-developed concepts for NIDCR initiatives for Council’s discussion, review, and approval and for public comment. Staff presented one concept, and three designated Council members led the discussion.
Collaborative Activities to Promote Research in Aging and Oral Health
Dr. Dena Fischer, director of the CCR’s Clinical and Practice-based Research Program, DER, presented a proposed initiative to accelerate research that will improve the oral health of older adults by addressing knowledge gaps in the etiology and management of dental, oral, and craniofacial (DOC) diseases associated with aging. She stated that the proposed concept, which follows on informal discussions with the Council at its May 24, 2016, meeting, would strongly encourage research proposals for interdisciplinary collaborations between researchers studying DOC health and disease and those studying aging. As background, Dr. Fischer noted that older adults comprise a rapidly growing segment of the U.S. population and that chronic diseases associated with aging can negatively affect oral health. More adults are retaining their natural dentitions throughout life; oral conditions such as periodontal disease, root caries, and salivary hypofunction are more common in older adults; and the risk of developing oral cancer increases with age. Dr. Fischer emphasized the need to better understand the basic biology of aging in DOC tissues versus aging in other tissues of the body; the impact of age-related changes on the oral environment and development of DOC disease; and relationships among aging, chronic disease, and oral conditions common in older adults.
To fill knowledge gaps, research is needed, for example, to identify genetic/genomic, molecular, and cellular mechanisms of healthy aging, wound healing/tissue regeneration capacity, and response to treatment in DOC tissues. Research is also needed to assess the impact of age-related biological changes in oral microbiota and/or oral immune function, salivary gland structure, and salivary composition upon the development of DOC disease. Improved model systems also are needed to study DOC tissues in aging and to compare these tissues to aging tissues and organs in other body regions. Longitudinal studies of cohorts of older adults with chronic disease would be useful for assessing oral disease prevention methods and treatment outcomes, as well as mechanisms of action in changing oral health behaviors among older adults.
The Council’s lead discussants, Dr. Yang Chai, Dr. Richard Darveau, and Dr. Jane Weintraub, strongly supported the concept. Dr. Chai suggested that the concept incorporate oral health research in vulnerable populations, such as older immigrants and those at low socioeconomic levels. He also suggested focusing the concept on a few areas (e.g., head and neck cancer, behavioral and social science research to increase access to care, the oral microbiome, and bone-related diseases) to make an impact, and he noted that the proposed initiative presents an opportunity for collaboration with other NIH institutes and centers. Dr. Darveau agreed with Dr. Chai and suggested that special emphasis be given to research aimed at understanding the etiology and management of oral diseases in older individuals.
Dr. Weintraub noted the paucity of research on oral health in aging, the disparities in oral health shown in data for older people, and the need to enhance understanding of oral health status and oral health-related quality of life in older people. She noted that with dramatic declines in edentulism, people are living longer with more teeth and are taking more medicines which may have oral effects (e.g., dry mouth) and increase the complexity of oral health in aging. Dr. Weintraub referenced an article in The Lancet which reported that more than one-half of babies who are born in rich countries since 2000 will live 100 years [“Aging Populations: The Challenges Ahead,” by K. Christensen and others, The Lancet 374 (9696):1196‒1208, 2009]. She specifically suggested that the proposed concept encourage both collaboration of oral health researchers with other researchers in aging and support for training and education of dental scientists in oral health and aging. Specific areas of study could include the intertwining of oral health and systemic health in older individuals; clinical, translational, epidemiological, and health services research on factors affecting these individuals’ access to care; research on dental aspects of health and well-being and comparison with other findings in this area; and the role of caregivers and health professions in assuring oral health in aging.
Dr. Fischer thanked the discussants and noted two themes—basic science to tease out DOC mechanisms and processes in aging, and clinical research to untangle the complex of aging, chronic disease, and effects on oral health. In discussion, the Council agreed with the discussants’ comments. Members highlighted the need for innovation in the delivery of oral health care, the importance of oral health to general health, and the need to expand and improve care for an increasingly aging population. The Council agreed that expansion of the concept to highlight specific areas would be helpful. Additional areas to cite could include oral health quality of life, changes in pain with aging, specific oral health issues among minority populations and other underserved groups (e.g., rural populations), and gender differences in aging and their effects on the need for and delivery of oral health care.
Dr. Somerman thanked the Council for its input in developing and discussing the concept. She noted that the initiative needs to be sufficiently broad, yet not too broad, to encourage meritorious proposals. The NIDCR will continue to work with Council members to refine the concept further.
The Council unanimously approved the concept.
VII. SPECIAL SESSION ON BIOMEDICAL IMAGING
Dr. Dombroski opened the special session on biomedical imaging. The session consisted of an introduction and overview of NIDCR’s commitment to this research area and three presentations on imaging modalities for craniofacial surgery, modeling, and research.
Dr. Orlando Lopez, director of the Dental and Biomaterials Program, IBIDB, DER, introduced the three guest speakers. He noted that all are world-renowned bioimaging scientists and would address the state of the art in biomedical imaging and emerging trends in DOC applications. The first speaker, an NIDCR grantee, was Dr. John V. Frangioni, Chief Executive Officer, Curadel, LLC, Marlborough, Massachusetts, and Professor Emeritus, Harvard Medical School, Cambridge, Massachusetts. The second speaker, also an NIDCR grantee, was Dr. James J. Xia, Director, Surgical Planning Laboratory, Department of Oral and Maxillofacial Surgery, Houston Methodist Research Institute, Houston, Texas; Professor, Institute for Academic Medicine, Houston Medical Hospital, Houston, Texas; and Professor of Oral and Maxillofacial Surgery, Weill Medical College of Cornell University, New York, New York. The third speaker was Dr. Denise K. Liberton, an NIDCR postdoctoral fellow in DIR’s Craniofacial Anomalies and Regeneration Section.
Dr. Lopez emphasized NIDCR’s commitment to supporting innovation in biomedical imaging. He summarized technical considerations in biomedical imaging and capabilities of different modalities, NIDCR’s portfolio of research on imaging, use of biomedical imaging in clinical trials, and future priority areas. He noted that biomedical imaging, as a guide to patient care and essential to biomedical research, is the fastest growing sector in medical expenditures and plays a central role in medical decision making for diagnosis, treatment, and understanding of a wide range of diseases and conditions.
The technical challenges in utilizing biomedical imaging include spatial and temporal resolution, artifacts, hardware limitations, and staffing (i.e., the need for well-trained clinicians, engineers, and technicians). Mainstream medical imaging modalities, which rely on different sources of energy and are used to visualize different types of tissues and organs in clinical settings, include computerized tomography (CT), magnetic resonance imaging (MRI), functional MRI (fMRI), nuclear technology [e.g., positron emission technology (PET)], and single-photon emission computed tomography (SPECT).
Dr. Lopez noted that the NIDCR portfolio of research in biomedical imaging, which comprises approximately 100 projects, is divided among imaging applications to detect and monitor disease (41 percent of projects), novel applications of existing imaging approaches (31 percent), and development of new imaging modalities (28 percent). Approximately 65 percent of the total portfolio is funded through research project grants (RPGs), and other mechanisms support the remaining projects (approximately 15 percent are SBIR awards, 6 percent are contract awards, and 10 percent are training grants). Dr. Lopez said that there has been a steady increase in funding for SBIR awards, amounting to approximately $5 million per year between FY 2014 and FY 2016. One SBIR/STTR award, for example, supports imaging diagnostics of dental diseases and conditions (caries, periodontal disease, cracked teeth, and pulp vitality).
Dr. Lopez highlighted three NIDCR-funded projects. In one, researchers are using optical imaging (near-infrared imaging and optical coherence tomography) to detect caries, define interactions between biofilm and dental composites, and better understand the enamel‒dentin structure. In a second, scientists are using novel imaging techniques to better understand the landscape of the oral microbiome (both beneficial and harmful microbes) and interactions between microbial communities. In a third, investigators are exploring use of a pen-sized, handheld microscope for point-of-care detection of oral and pharyngeal cancer.
Future priority areas in which the NIDCR is involved include use of biomedical imaging in clinical trials, advancing the capabilities of biomedical imaging, and applications across the patient healthcare continuum (from patient referrals to scanning, interpretation of scans, and follow up). Dr. Lopez noted that establishing the safety and effectiveness of products and devices would be enhanced by ensuring optimal quality of imaging data and reducing variability among data by standardizing the imaging process. To foster standardized processes, application of quantitative approaches including big data and data science concepts to medical imaging, and improved translation of new imaging technologies into patient care, the Congress established in December 2016 the Interagency Working Group on Medical Imaging. This working group offers guidance on coordinating use of medical imaging for better health outcomes and scientific discovery.
VIII. INVISIBLE NEAR-INFRARED LIGHT FOR CRANIOFACIAL SURGERY AND BIOMEDICAL RESEARCH
Dr. Frangioni thanked the NIDCR for the opportunity to present his research to the Council. He described the special advantages of near-infrared (NIR) light as an imaging modality, systems and contrast agents used, applicability of NIR light in craniofacial research, and clinical examples of using NIR light for craniofacial surgery.
The advantages of using NIR light include its minimal photon absorption, photon scatter, and autofluorescence and its invisibility to the human eye. Among imaging modalities, only NIR light provides high contrast, does not change the look of the field of view, can potentially highlight any object, and offers real-time intraoperative imaging and millimeter depth detection, as well as no exposure to ionizing radiation. Dr. Frangioni noted that, during surgery, NIR light could be used for sensitive, real-time, high-resolution detection of tumor margins (detection of single-cell tumors is already feasible); avoidance of vital structures such as blood vessels and nerves during tumor resection without need for ionizing radiation; prediction of future tissue viability in real-time with or without contrast and for days and weeks after surgery; and longitudinal assessment of tissue remodeling and regeneration with and without modulating drugs. The hope is to ultimately improve surgical outcomes, lower health care costs, and improve human health. He noted that proof of principle has been established for use of NIR light with exogenous NIR fluorescence in more than 1,000 patients worldwide (500 patients using the FLARE® imaging systems) and with endogenous NIR light in more than 10,000 patients.
Dr. Frangioni briefly described FLARE® (Fluorescence-Assisted Research and Exploration)—a platform technology using invisible NIR fluorescent light to identify and quantify objects in in vitro and in vivo systems. He noted that the unified FLARE® software interface would enable surgeons to perform precision surgery with real-time imaging guidance. With NIDCR support, his team has compared two technologies: exogenous NIR fluorescence with contrast media (indocyanine green) and endogenous NIR quantitation.
Dr. Frangioni elaborated on use of NIR light in craniofacial research. Using a model of face transplant in swine, his team has shown that endogenous NIR quantitation can be used to assess in real-time the viability of a face transplant, to prevent failure. Research applications using exogenous NIR fluorescence with FLARE® systems and optimized contrast agents include in vivo and in vitro detection and quantitation of cartilage formation and destruction, as well as single live-cell tracking of cancer and immune cells, thus allowing for improved tissue engineering, remodeling, and regeneration. By marrying NIR light with histofluorescence tomography (HFT), researchers also can now perform single-cell, 3-dimensional (3D) analysis of macroscopic structures in entire animals—for example, to understand lymphatic flow in the head and neck microscopically.
Dr. Frangioni noted that FLARE® imaging systems have been and are being used in clinical trials. More than 700 patients have been studied worldwide by independent research groups in various countries, and the results have been published in peer-reviewed journals. Current Lab-FLARE® systems are in the fourth generation, and there were no safety issues in the first three generations. Two examples of their clinical use in craniofacial surgery are real-time detection and resection of neck tumors and sentinel lymph node mapping of the head and neck. Methylene blue and indocyanine green were used, respectively, as contrast agents in these studies, as approved by institutional review boards.
Dr. Frangioni said the possibilities of agents and antibodies that could be used with NIR light for research and clinical translation are unlimited and that he has used more than 40 agents in his own research. Future possibilities for using either NIR light with exogenous or endogenous fluorescence are very promising. With exogenous fluorescence, basic research will continue on tissue engineering and regeneration and stem cell tracking, while clinical studies continue to explore tumor resection, normal tissue avoidance, prediction of tissue viability, and tissue transplants. With endogenous fluorescence, the basic science will focus on tissue oxygenation, hydration, and metabolism, while clinical translation will focus on large field-of-view oximetry and real-time assessment of tissue status. The future of head and neck surgery will include dual-NIR channel imaging of the parathyroid and thyroid glands, simultaneous imaging of bone and intervertebral discs, and predicting future tissue viability and improving outcomes of facial transplants.
In closing, Dr. Frangioni expressed gratitude to his research collaborators and to the NIDCR for its support. He provided a list of published reviews of this research and referred the Council to a resource-sharing portal at http://curadel.com/home/resource-sharing. In discussion, he noted that NIR light, a near-the-surface imaging modality, will not supplant use of x-rays.
IX. PAST, PRESENT, AND FUTURE OF COMPUTER-AIDED SURGICAL STIMULATION FOR CRANIOMAXILLOFACIAL (CMF) SURGERY
Dr. Xia thanked the NIDCR for the opportunity to present his research to the Council. He dedicated his presentation to the memory of Dr. William H. Bell (1927‒2016), who pioneered orthognathic surgery and use of computer-assisted design in surgery.
Dr. Xia described the craniomaxillofacial (CMF) research underway in the Surgical Planning Laboratory (SPL) at Houston Methodist Research Institute. He noted that the patient is at the center of this research and that the ultimate goal is to significantly improve the quality of patient care by identifying clinical problems in patients’ treatment and solving them through cutting-edge research. SPL researchers have been studying computer-aided surgical simulation (CASS) and image-guided surgery for distraction osteogenesis, bone regeneration, temporomandibular joint disorders, craniosynostosis, and cleft lip and palate.
Dr. Xia specifically addressed orthognathic surgery for severe jaw deformities. He noted that the success of any CMF reconstruction depends on careful pre-surgical evaluation—to gain a 3D understanding of the deformity, develop an optimal surgical plan, precisely execute the plan during surgery, and provide good postoperative care. He noted also that the planning of CMF surgeries has not changed much since the 1960s and too often still relies on x-rays, cephalometry and prediction tracing on paper, and articulation with stone models to establish a final occlusion on which to prepare a surgical splint. He said that using this method, “sometimes we get lucky, but sometimes we don’t.” He called for a paradigm shift to promote use of the CASS approach.
Dr. Xia noted that the first CASS clinical protocol was reported in 2009 and then improved with 3D cephalometry in 2015. The current protocol incorporates computer-aided modeling, planning, preparing for plan evaluation, and outcome assessment. He described and illustrated, with schematics and patient profiles, the benefits of CASS at each of these stages. Since development of the CASS protocol, a number of studies have been completed to show that CASS fulfills all the parameters of an “engineering adage”—that is, a new technology should be more accurate, achieve a better outcome, be more effective, or achieve things not achievable previously (be a new paradigm shift). Dr. Xia reported that surgical outcomes achieved with the CASS protocol are comparable to planned outcomes and are significantly better than those achieved using traditional methods. Evidence of the benefits of using the CASS protocol is well documented in many evaluation studies cited in PubMed.
Dr. Xia noted that although CASS has been proven to be the standard of care for CMF surgery, many U.S. and international surgeons are still using the problematic traditional planning method in their practices. He emphasized the need to promote surgeons’ access to the CASS protocol by disseminating information about it more broadly and by engaging industrial partners, who are critically needed to assure that the CASS protocol becomes the standard of care for all CMF surgeries.
Dr. Xia noted that within the near future, preoperative surgical planning will include use of scanners, software for artificial intelligence-based virtual surgical planning, and affordable in-house 3D printers. His research team is developing cutting-edge CASS technology that relies on use of cell phones and free, user-friendly software to make surgical planning as simple as possible. The software will support efficient segmentation, true 3D cephalometry, automatic anatomical landmark digitization and digital dental articulation, accurate facial and tissue stimulation, and design of surgical splints and templates for in-house 3D printing. Dr. Xia illustrated how this precision, or personalized, medicine approach will enable CMF surgeons to do facial shape-based surgical planning digitally, streamline their surgery protocol according to symmetry and facial form, predict changes in facial soft tissues, and streamline the design of surgical splints or templates. Further, with in-house 3D printing, all of this becomes possible in an office setting.
In closing, Dr. Xia acknowledged his colleagues and collaborators and said that a resource-sharing portal (www.AnatomicAligner.org) is being developed and will be linked with the NIDCR webpage.
X. 3D IMAGING AND PREDICTIVE MODELING IN RARE AND COMMON CRANIOFACIAL ANOMALIES
Dr. Liberton thanked the Council for the opportunity to present NIDCR research on dental and craniofacial imaging. She noted the variety of imaging technologies in use, including panoramic dental x-rays, lateral cephalograms, MRI, cone-beam computed tomography (CBCT), stereophotogrammetry, micro-computed tomography (ųCT), and scanning electron microscopy. Dr. Liberton focused on her laboratory’s research with CBCT. She elaborated on each of the following three goals of the laboratory: to provide new 3D skeletal normative data for clinical and research purposes, to develop predictive models for craniofacial growth, and to apply these methods to better characterize rare diseases.
With regard to the first goal (provide 3D skeletal normative data), Dr. Liberton noted that 2D cephalometric norms have been available for more than 60 years and, though useful, are imperfect for surgery planning and are being replaced by 3D soft-tissue facial norms. However, 3D skeletal norms for CBCT and other imaging technologies are lacking, and her laboratory and other groups are working to fill this gap in knowledge with quantitative information. Using CBCT, new 3D skeletal landmarks have been derived and validated in limited cohorts, but the information on age, sex, and ethnic variation remain inadequate and the information on asymmetry is lacking. She noted that NIDCR researchers have defined 64 cranial base landmarks, which would allow for quantification of asymmetry in development of the cranial base and localization of cranial base growth. They are currently working to validate this landmark set in a cohort of approximately 500 individuals of varying ages, sexes, and ethnicities, from age 10 to adulthood. Similar to Dr. Xia’s work, they are also exploring automatic CT-based skeletal segmentation and definition of landmarks in skeletal variability.
With regard to the second goal (develop predictive models), Dr. Liberton said her team is developing population-wide and patient-cohort predictive models of craniofacial growth. The researchers are looking at dento-facial deformities in 3D and, specifically, the non-syndromic growth variants (class I‒III) which occur in a significant number of patients. The aim is to be able to predict patients who will need surgical reconstruction as they grow. The researchers are also studying teenage patients in the NIDCR dental clinic in hopes of predicting skeletal growth curves to identify deformities earlier than now possible so that they could be treated with orthodontic intervention sooner rather than surgery later. In addition, the researchers are looking at morphological integration of the cranial base in order to develop a database of the class I‒III patients—to study the relationship between craniofacial morphology and other bony structures and to better understand growth and development of the entire skull.
With regard to the third goal (better characterize rare diseases), Dr. Liberton noted that rare diseases are poorly understood and that modeling and imaging could provide quantitative data on skeletal or soft-tissue shape to predict disorders and/or mutations—information that would be useful for developing better treatment planning tools. She said the challenges in working on rare diseases are particularly difficult because of unknown alterations in craniofacial growth curves and high phenotypic variability within and across diagnoses. The NIDCR researchers hope to build a database in collaboration with patients. Dr. Liberton elaborated on the potential contribution of 3D imaging in patients with Loeys-Dietz Syndrome (LDS), a connective tissue disorder that was first described in 2006 and is due to autosomal dominant mutations in the transforming growth factor beta (TGF-ß) pathway controlling morphogenesis and development of the neural crest. She reported that the 3D CBCT image analysis is providing quantitative data to support clinical findings, showing variations in the skull that may not be revealed by clinical exam, and helping researchers to better understand differences in patient types and phenotypic differences vis-à-vis norms and to make hypotheses and predictions about developmental alterations. This clinical research is complemented by ųCT analysis in LDS mouse models.
Dr. Liberton said that future directions in the laboratory’s research include continued development of a database of craniofacial morphology—to better evaluate craniofacial growth and morphology at different ages, predict diagnoses based on shape classifications, predict “normal” shape for surgery planning purposes, and identify subclinical variations among patients. The laboratory hopes to build up this database in collaboration with other NIH scientists and extramural researchers. In closing, she acknowledged and thanked the NIDCR and other scientists who are collaborating in this research.
XI. QUESTIONS AND DISCUSSION
In discussion, Dr. Liberton responded to several questions specific to her research and the potential for collaboration with the NIDCR-supported FaceBase Consortium.
Dr. Dombroski and the Council thanked the speakers for their presentations.
XII. ADJOURNMENT OF OPEN SESSION
Dr. Somerman adjourned the open session of the Council meeting at 12:04 p.m.
This portion of the meeting was closed to the public in accordance with the determination that it was concerned with matters exempt from mandatory disclosure under Sections 552b(c)(4) and 552b(c)(6), Title 5, U.S. Code and Section 10(d) of the Federal Advisory Committee Act, as amended (5 U.S.C. Appendix 2).
XIII. REVIEW OF APPLICATIONS
The Council considered 438 applications requesting $108,421,529 in total costs. The Council recommended 264 applications for a total cost of $63,365,525 (see Attachment II).
The meeting was adjourned at 2:13 p.m. on January 24, 2017.
I hereby certify that the foregoing minutes are accurate and complete.
Dr. Martha J. Somerman, Chairperson
Dr. Alicia Dombroski, Executive Secretary
National Advisory Dental and Craniofacial Research Council