RESEARCH AND DEVELOPMENT OF SYSTEMS AND METHODS FOR MOLECULAR IMAGING RELEASE DATE: February 12, 2002 RFA: RFA-EB-02-001 PARTICIPATING INSTITUTES AND CENTERS (ICs): National Institute of Biomedical Imaging and Bioengineering (NIBIB) (http://www.nibib.nih.gov) National Human Genome Research Institute (NHGRI) (http://www.nhgri.nih.gov/) LETTER OF INTENT RECEIPT DATE: March 29, 2002 APPLICATION RECEIPT DATE: April 24, 2002 THIS RFA CONTAINS THE FOLLOWING INFORMATION: o Purpose of this RFA o Research Objectives o Funds Available o Eligible Institutions o Individuals Eligible to Become Principal Investigators o Where to Send Inquiries o Letter of Intent o Submitting an Application o Peer Review Process o Review Criteria o Receipt and Review Schedule o Award Criteria o Required Federal Citations PURPOSE OF THIS RFA The National Institute of Biomedical Imaging and Bioengineering (NIBIB) and the National Human Genome Research Institute (NHGRI) invite applications for NIH Research Project Grant (R01) awards to support interdisciplinary basic research or Phased Innovation (R21/R33) awards to support novel investigations for molecular imaging and spectroscopy development that can be broadly applied to research on biological or disease processes. The primary focus of this Request for Applications (RFA) is in vivo molecular imaging and/or spectroscopy including devices, methods, and contrast agents for biomedical research and human investigations. The integration of these systems and methods with other imaging/spectroscopy modalities is also included as appropriate to support clinical investigations. Consistent with the mission of the NIBIB, this initiative supports discovery or development of cross- cutting technologies for molecular imaging and/or spectroscopy systems and methods that can be broadly applied to research on biological or disease processes. The motivation for this Request for Applications is that discoveries in molecular and cellular biology present extraordinary opportunities for biomedical imaging to play an important role in the early detection, diagnosis, and treatment of disease. Since current molecular-level technologies primarily focus on in vitro methods, there is a need to support new technologies that allow high spatial and temporal resolution in vivo imaging and/or spectroscopy methods close to the cellular or molecular scales for clinical or research investigations. Another need is for new technologies that can improve the sensitivity and specificity for the measurement of molecular signatures associated with different disease processes. The NIBIB seeks to improve health by promoting fundamental discoveries, design and development, and translation and assessment of technological capabilities in biomedical imaging and bioengineering enabled by relevant areas of physics, chemistry, mathematics, engineering, materials science, and computer science. RESEARCH OBJECTIVES The need to support discovery and development of biomedical imaging methods has been identified at several NIH workshops and conferences on biomedical imaging including a June 25-26, 1999, symposium titled "Biomedical Imaging Symposium: Visualizing the Future of Biology and Medicine" which was coordinated by the NIH Bioengineering Consortium (BECON). Three scientific areas were addressed (1) imaging at the cellular- and molecular-levels such as required for the early detection of disease, (2) imaging for the clinical diagnosis, staging, and recurrence of disease, and (3) imaging applied to therapeutic applications and monitoring for various disease processes. The development of novel molecular imaging/spectroscopy methods that improve the spatial and temporal resolution, measurement sensitivity, and specificity for all three areas was identified as a critical need for this field. Molecular information was recognized as having a profound impact on our approach for diagnosing and treating diseases that have the potential of being redefined in terms of their characteristic genetic or molecular abnormalities. New forms of therapy are possible to target the abnormal gene or phenotypic pathway, and methods are needed for image guidance to track response to these new therapeutic strategies. These advances are critically related to the development of molecular probes and contrast agents that can provide the associations to specific biological processes and thus improve the sensitivity and specificity of imaging methods for early disease detection and monitoring of therapeutic response. Optimization of imaging systems and methods is required to realize the full potential of new contrast agents. This BECON symposium also emphasized the need to support fundamental discovery and technical development of imaging technologies before specific disease- or organ-oriented applications are determined. These challenges can effectively be accomplished by multi-disciplinary teams from academia, national laboratories, and industry, with expertise in the quantitative, computational, and biomedical sciences. In addition, the needs for appropriate research support mechanisms and NIH study section reviews that emphasize technology development with less emphasis on organ- or disease-specific clinical applications were identified. Consistent with the recommendations of the BECON symposium and the mission of the NIBIB, the goals of this RFA are directed at basic research and/or development of in vivo molecular imaging/spectroscopy systems. Research areas of interest include methods and contrast agents that enhance spatial or temporal resolution, measurement sensitivity, and specificity as required for the detection, diagnosis, or measurement of treatment efficacy for different disease processes. The scope of the RFA includes the integration of these systems and methods with anatomical or other functional imaging/spectroscopy methods to provide more effective tools for clinical use, the development of imaging or spectroscopy systems that have the flexibility to accommodate a variety of protocols for investigations of different diseases, and the development of platform-independent imaging methods for multi-center research. These systems, methods, and applications must be designed for eventual clinical use. Development of in vitro imaging/spectroscopy systems and methods will only be considered responsive to this RFA if they are required to validate in vivo imaging/spectroscopy systems and methods. Feasibility studies or proof-of-principal studies are appropriate to demonstrate the potential of the proposed systems and methods. The following research areas are examples of appropriate topics for applications in response to this RFA. This list is meant to be representative and not all inclusive: o Discovery and development of the next generation of in vivo molecular imaging and/or molecular spectroscopy systems and methods. The research scope may include high-risk, high-gain research objectives such as new in vivo imaging and/or spectroscopy paradigms using tomographic, stationary, image-guided, or implanted systems and methods. Mathematical modeling of such systems and their performance is included as required for system optimization. System optimization for contrast agents and molecular probes can also be addressed where appropriate. The use of endogenous and other contrast mechanisms may be included provided these methods complement molecular imaging/spectroscopy methods. Areas of interest also include image and data processing provided the objective of this research complements molecular methods. o Development and system integration of molecular imaging and/or molecular spectroscopy systems with other imaging or spectroscopy systems and methods, namely multi-modality imaging (e.g., to include tomographic and other localized stationary, image guided, or implanted sensors). Development of sensors or multiple sensors that take advantage of Micro Electrical and Mechanical Systems (MEMS) and Nano Electrical and Mechanical Systems (NEMS) technologies are included. Possible research examples include image and data processing, image display, and image archiving provided the objectives of this research complement molecular methods. Applications of these systems may include early detection, diagnosis, computer-assisted or image-guided intervention or therapy, and measurement of response to therapy for different organ systems and diseases. o Discovery and development of the next generation of contrast agents for in vivo molecular imaging and/or spectroscopy methods. These may include the development of molecular probes for biological processes such as gene expression at the level of transcription or translation, signal transduction for cell surface receptors, enzyme action or other metabolic processes, or blood flow or drug action that may impact the study of several disease processes. Single or multiple contrast agents or contrast agents suitable for multi-modality imaging/spectroscopy are included. Combinatorial chemistry for contrast agent development or nanoparticles for contrast agent delivery systems or therapeutic applications are also included. MECHANISM OF SUPPORT This RFA will use the NIH Research Project Grant (R01) and Phased Innovation Award (R21/R33) mechanisms. As an applicant, you are solely responsible for planning, directing, and executing the proposed project. This RFA is a one-time solicitation. Future unsolicited, competing-continuation applications based on this project will compete with all investigator-initiated applications and will be reviewed according to the customary peer-review procedures. The anticipated award date is September 30, 2002. This RFA uses just-in-time concepts. Applications for R01 grants use the modular as well as the non-modular budgeting formats (see http://grants.nih.gov/grants/funding/modular/modular.htm). Specifically, if you are submitting a R01 application with direct costs in each year of $250,000 or less, the modular format should be used. Otherwise, follow the instructions for non-modular research grant applications. For this RFA, applications for R21/R33 grants should use the detailed budget (non-modular) format only. The R01 mechanism is recommended for applications that emphasize basic discovery or cross-cutting research that addresses specific aspects of imaging systems, methods, or contrast agents. Research periods associated with the R01 proposals are limited to five years. The R21/R33 Phased Innovation Award is recommended for system engineering approaches such as the development and integration of imaging tools or agents, or partnerships with industry for technology development and dissemination. The combined R21/R33 application offers two advantages over the regular application process (1) single submission and evaluation of both the R21 and R33 phases as one application and (2) minimal or no funding gap between the R21 and R33 phases. A single application for the combined R21 and R33 phases with a total period of up to five years is required for this initiative. The R21 phase supports exploratory or developmental research aimed at proof-of-principle for high-risk projects where preliminary data is not available. An R21 application can be for one to two years with a maximum budget request of $150,000 direct costs per year. The R33 mechanism supports the second phase of the innovative exploratory or developmental research initiated under the R21 mechanism. A R33 application can be for one to four years. Transition from the R21 to the R33 phase is dependent on successful completion of milestones specified in the R21 application as determined by program staff. Applicable recommendations from the peer review of the R21/R33 application will be followed in this determination. The R21 application must include milestones that will be used to judge the success of the proposed exploratory research. The Phased Innovation Award application must have a section titled "Milestones" at the end of the Research Plan for the R21 application. This section must propose well-defined, quantifiable milestones for the completion of the R21 phase, a discussion of the suitability of the proposed milestones for assessing the success of the R21 research, and a discussion of the implications of successful completion of these milestones for the R33 phase. FUNDS AVAILABLE The NIBIB and the NHGRI intend to commit approximately $5.2 million in FY 2002 to fund 10 to 20 new grants in response to this RFA. Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the FY 2002 financial plans of the NIBIB and the NHGRI provide support for this program, awards pursuant to the RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. At this time, it is not known if this RFA will be reissued. ELIGIBLE INSTITUTIONS You may submit an application if your institution has any of the following characteristics: o For-profit or non-profit organization o Public or private institutions such as universities, colleges, hospitals, and laboratories o National laboratories o Units of State and local governments o Eligible agencies of the Federal government o Domestic or foreign INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from under-represented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH programs. WHERE TO SEND INQUIRIES We encourage inquiries concerning this RFA and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial/grants management issues. o Direct questions regarding programmatic issues to: Dr. Richard E. Swaja Acting Director of the Division of Biomedical Imaging National Institute of Biomedical Imaging and Bioengineering Building 31, Room 1B37 Bethesda, MD 20892-2077 Telephone: 301-451-6768 Fax: 301-480-4515 Email: swajar@nibib.nih.gov Dr. Jeffery A. Schloss Division of Extramural Research National Human Genome Institute Building 31, Room B2B07 Bethesda, MD 20892-2033 Telephone: 301-496-7531 Fax: 301-480-2770 Email: jeff_schloss@nih.gov o Direct questions about peer review issues to: Dr. Lee Rosen Scientific Review Administrator Center for Scientific Review 6701 Rockledge Drive, Room 5116 Bethesda, MD 20892 Telephone: 301-435-1171 Fax: 301-480-2644 Email: rosenl@drg.nih.gov o Direct questions regarding fiscal matters to: Ms. Annette Hanopole Grants Management Officer National Institute of Biomedical Imaging and Bioengineering Building 31, Room 1B37 Bethesda, MD 20892-2077 Telephone: 301-451-6768 Fax: 301-480-4515 Email: hanopola@nibib.nih.gov Ms. Jean Cahill Grants Administration Branch National Human Genome Research Institute Building 31, Room B2B34 Bethesda, MD 20892-2031 Telephone: 301-402-0733 Fax: 301-402-1951 Email: jc166o@nih.gov LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes the following information: o Number and title of this RFA o Descriptive title of proposed research o Name, address, phone number, and e-mail address of the principal investigator o Names of other key personnel o Participating institutions Although a letter of intent is not required, is not binding, and does not enter into the review of the subsequent application, the information that it contains allows NIBIB and CSR staff to estimate the potential review workload and to plan the review. The letter of intent is to be sent by the date listed at the beginning of this document. It is preferred that the letter of intent be sent electronically to noi@nibib.nih.gov. If necessary, the letter of intent can be sent by regular mail to the scientific/research contact listed in the WHERE TO SEND INQUIRIES section of this announcement. SUBMITTING AN APPLICATION Applications must be prepared using the PHS 398 research grant application instructions and forms (rev. 5/2001, updated 5/2002). The PHS 398 is available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. For further assistance, contact GrantsInfo at (301-710-0267 or GrantsInfo@nih.gov. SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS: Applications requesting up to $250,000 per year in direct costs must be submitted in a modular grant format. The modular grant format simplifies the preparation of the budget in these applications by limiting the level of budgetary detail. Applicants request direct costs in $25,000 modules. Section C of the research grant application instructions for the PHS 398 (rev. 5/2001, updated 1/2002) at http://grants.nih.gov/grants/funding/phs398/phs398.html includes step- by-step guidance for preparing modular grants. Additional information on modular grants is available at http://grants.nih.gov/grants/funding/modular/modular.htm. USING THE RFA LABEL: The RFA label available in the PHS 398 (rev.5/2001, updated 5/2002) application form must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the "YES" box must be marked. The RFA label is also available at http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. SENIDNG AN APPLICATION TO THE NIH: Submit a signed, typewritten original of the application including the "Checklist" and five signed photocopies to: Center for Scientific Review National Institutes of Health 6701 Rockledge Drive, Room 1040, MSC 77l0 Bethesda, MD 20892-7710 or Bethesda, MD 20817 (for express/courier service) APPLICATION PROCESSING: Applications must be received at the NIH by the application receipt date listed in the heading of this RFA. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review will not accept any application in response to this RFA that is essentially the same as one currently pending initial review unless the applicant withdraws the pending application. The CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an "Introduction" that addresses the how comments from the previous critique have been addressed. PEER REVIEW PROCESS Upon receipt, applications will be reviewed for completeness by the CSR and for responsiveness by the NIBIB. Incomplete and/or non-responsive applications will be returned to the applicant without further consideration. Applications submitted in response to this RFA will be reviewed by special emphasis panels of the CSR in accordance with criteria specified in the following section. REVIEW CRITERIA The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of your application to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals: o Significance o Approach o Innovation o Investigator o Environment The Scientific Review Group will address and consider each of these criteria in assigning your application"s overall priority score, weighting them as appropriate for each application. Your application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, you may choose to carry out important work that by its nature is not innovative but is essential to move a field forward. (1) SIGNIFICANCE: Does the proposed study address an important cross- cutting discovery or technology/tool development with broad application to biological or medical processes? If the aims of your application are achieved, how will scientific knowledge be advanced? What will be the effects of these studies on the concepts and methods that drive the field? To what degree does the technology support the needs for research on biological or disease processes? (2) APPROACH: Are the conceptual framework, design, and methods adequately developed, well-integrated, and appropriate for (l) cross- cutting fundamental discovery (R01) or (2) technology and tool development (R21/R33)? Does the applicant acknowledge potential problem areas and consider alternative tactics? If appropriate, what is the time frame for developing the proposed technologies or tools, and what is the suitability of this time frame for meeting the community"s needs? How easy will it be to use the proposed technology or tools? Are the plans adequate for integrating the proposed technology as an effective solution for implementation and dissemination? If industrial partnerships are proposed, how will they facilitate and complement the technology and tool development? (3) INNOVATION: Does the project address discovery or technology/tool development that represents innovation for the field? Does the project challenge existing paradigms or employ novel concepts, approaches, or methods? What are the cross-cutting applications of the proposed fundamental discovery, technology, or tools? (4) INVESTIGATOR: Does the principal investigator possess appropriate experience and capabilities to direct and carry out this work? Is the experience level of the principal investigator, other researchers, or collaborators appropriate for the proposed effort? (5) ENVIRONMENT: Does the technical and scientific environment in which the work will be performed contribute to the probability of success? Are the resources adequate to support the proposed experimental program? Does the proposed work take advantage of unique features of the technical and scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support or collaborative agreements? ADDITIONAL REVIEW CRITERIA: In addition to the above criteria your application will also be reviewed with respect to the following: o MILESTONES FOR COMBINED R21/R33 APPLICATIONS: For the R21/R33 applications, how appropriate are the proposed milestones for evaluating the demonstration of feasibility for the R21 effort and transition to the R33 development phase? For R21/R33 Phased Innovation Award applications, the Initial Review Group will evaluate the specific goals of each phase and the feasibility milestones that would justify progression to the R33 phase. A single priority score will be assigned to each scored application. As with any grant application, the IRG has the option of recommending support for a shorter duration than that requested by the applicant, and basing the final merit rating on the recommended portion of the application. This may result in a recommendation that only the R21 phase of the combined R21/R33 application be supported based on the relative merit of the two research plans, adequacy of the milestones for determining success of the R21 feasibility studies, and capacity to provide easily assessed justification for progression to the R33 phase without further review. The IRG may recommend modifications to or the addition of milestones. Deletion of the R33 phase by the review panel or inadequate milestones may affect the rating of the application. o PROTECTIONS: The adequacy of the proposed protection for humans, animals, or the environment to the extent that they may be adversely affected by the project proposed in the application. o BUDGET: The reasonableness of the budget and the requested period of support in relation to the proposed research. RECEIPT AND REVIEW SCHEDULE Letter of Intent Receipt Date: March 29, 2002 Application Receipt Date: April 24, 2002 Peer Review Date: June/July 2002 Council Review: September 2002 Earliest Anticipated Start Date: September 30, 2002 AWARD CRITERIA Award criteria that will be used to make award decisions include: o Scientific merit as determined by peer review o Availability of funds o Programmatic priorities REQUIRED FEDERAL CITATIONS INCLUSION OF WOMEN AND MINORITIES IN CLINICAL RESEARCH: It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the AMENDMENT "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research - Amended, October, 2001," published in the NIH Guide for Grants and Contracts on October 9, 2001 (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html), a complete copy of the updated Guidelines are available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research, updated racial and ethnic categories in compliance with the new OMB standards, clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398, and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH- defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable, and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences. INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN SUBJECTS: The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all human subjects research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them. This policy applies to all initial (Type 1) applications submitted for receipt dates after October 1, 1998. All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects that is available at http://grants.nih.gov/grants/funding/children/children.htm. REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS: NIH policy requires education on the protection of human subject participants for all investigators submitting NIH proposals for research involving human subjects. You will find this policy announcement in the NIH Guide for Grants and Contracts Announcement, dated June 5, 2000, at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT: The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this RFA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site. HEALTHY PEOPLE 2010: The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This RFA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople. AUTHORITY AND REGULATIONS: These programs are described in the Catalog of Federal Domestic Assistance No. 93.286 (NIBIB) and No. 93.172 (NHGRI) and are not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies described at http://grants.nih.gov/grants/policy/policy.htm and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. The PHS strongly encourages all grant recipients to provide a smoke- free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


NIH Office of Extramural Research Logo
   Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS) 		  USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®