RELEASE DATE:  February 12, 2002

RFA:  RFA-EB-02-001


National Institute of Biomedical Imaging and Bioengineering (NIBIB)
National Human Genome Research Institute (NHGRI)




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


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.


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.

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  
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.


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.


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


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.


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

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

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	

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

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


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 
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  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.


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 in an 
interactive format.  For further assistance, contact GrantsInfo at 
(301-710-0267 or

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 includes step-
by-step guidance for preparing modular grants.  Additional information 
on modular grants is available at

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

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.

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.


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:

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.


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 that will be used to make award decisions include:

o Scientific merit as determined by peer review
o Availability of funds
o Programmatic priorities


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 
a complete copy of the updated Guidelines are available at  
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.

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

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

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

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.

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

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 
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.

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