CHARACTERIZING, VALIDATING, AND COMPARING NEUROIMAGING INFORMATICS TOOLS

Release Date:  December 6, 2001

RFA:  RFA-MH-02-008

National Institute of Mental Health
 (http://www.nimh.nih.gov/)
National Institute of Neurological Disorders and Stroke
 (http://www.ninds.nih.gov/)
National Institute of Biomedical Imaging and Bioengineering
 (http://www.nibib.nih.gov/)

Letter of Intent Receipt Date:  January 25, 2002
Application Receipt Date:       February 26, 2002

THIS RFA USES "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  MODULAR 
INSTRUCTIONS MUST BE USED FOR RESEARCH GRANT APPLICATIONS REQUESTING LESS THAN 
$250,000 PER YEAR IN ALL YEARS.  MODULAR BUDGET INSTRUCTIONS ARE PROVIDED IN 
SECTION C OF THE PHS 398 (REVISION 5/2001) AVAILABLE AT 
http://grants.nih.gov/grants/funding/phs398/phs398.html.

PURPOSE

Functional magnetic resonance imaging (fMRI) is increasingly important for 
understanding human brain function.  As with other imaging modalities, 
informatics tools are used at all stages of fMRI studies.  As fMRI has evolved 
in neuroscience laboratories, investigators have created informatics tools to 
allow them to address particular research questions.  This has resulted in a 
relatively small number of informatics tools that are both useful and widely 
used.

Despite the utility and popularity of particular informatics tools, however, 
these tools are often poorly characterized, and few studies have been 
conducted to validate their use for particular purposes or to compare 
rigorously different tools used in fMRI.  The National Institute of Mental 
Health (NIMH) and the National Institute of Neurological Disorders and Stroke 
(NINDS) solicit applications for grants to support such studies of informatics 
tools used widely in fMRI studies of the brain, and/or to support the 
development of the means to carry out such studies.  Although the mission of 
the National Institute of Biomedical Imaging and Bioengineering (NIBIB) does 
not focus on tools used primarily to study a single organ system, such as the 
brain, NIBIB solicits applications for grants to support more fundamental work 
on the assessment of biomedical technologies, including the characterization, 
validation, and comparison of informatics tools used across multiple 
modalities and multiple organ systems, which may include the brain.

This solicitation is an activity of the Neuroimaging Informatics Technology 
Initiative (NIfTI), which supports targeted and coordinated service, training, 
and research to enhance the use, and speed the development, of informatics 
tools for neuroimaging.  The initial focus of NIfTI will be on informatics 
tools used in fMRI studies.

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 Request for Applications (RFA), 
Characterizing, Validating, And Comparing Neuroimaging Informatics Tools, 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/.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the Federal government.  Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as Principal 
Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) research project 
grant (R01) award mechanism.  Responsibility for the planning, direction, and 
execution of the proposed project will be solely that of the applicant.  The 
total project period for an application submitted in response to this RFA may 
not exceed 4 years.  This RFA is a one-time solicitation.  Future unsolicited 
competing continuation applications will compete with all investigator-
initiated applications and be reviewed according to the customary peer review 
procedures.  The anticipated award date is September 30, 2002.

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts that have been adopted by the 
NIH.  Complete and detailed instructions and information on Modular Grant 
applications have been incorporated into the PHS 398 (rev. 5/2001).  
Additional information on Modular Grants can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm.

FUNDS AVAILABLE 

The participating Institutes intend to commit approximately $1.75 million in 
FY 2002 to fund 5 to 7 new and/or competitive continuation grants in response 
to this RFA.  An applicant may request a project period of up to 4 years. 
Because the nature and scope of the research proposed may vary, it is 
anticipated that the size of each award will also vary.  Although the 
financial plans of the NIMH, NINDS, and NIBIB provide support for this 
program, awards pursuant to this 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.

RESEARCH OBJECTIVES

Background

Over the past decade, functional magnetic resonance imaging (fMRI) has assumed 
a critical role in understanding human brain function at the level of neural 
systems.  This role has been enhanced due to recent scientific and technologic 
advances such as the development of compatible modalities (e.g., diffusion 
tensor MRI), the adoption of higher field MRI instruments for fMRI studies, 
and a better understanding of the relationship between electrophysiological 
activity and the blood-oxygen-level-dependent (BOLD) signal, which is widely 
used in fMRI studies of brain function.

Informatics tools are key to all stages of fMRI neuroimaging, they are crucial 
both to performing neuroimaging studies and to understanding the results of 
such studies.  The conclusions drawn from fMRI studies regarding the 
relationship between functional activation signals and function of the brain 
should be based upon a clear understanding of the manner in which various 
tools affect the data at each stage of processing.  Knowing that the 
operations performed by informatics tools are valid is also of obvious 
importance to interpreting the results of fMRI studies.  Finally, comparing 
different tools to identify the conditions under, and uses to which they are 
best suited is significant information that neuroscientists using fMRI would 
welcome.  Nevertheless, there is a dearth of published information about any 
of these very fundamental aspects of such informatics tools.  The reasons for 
this are several, but the lack of impact that such information would have on 
progress in human neuroscience is not one of them.

Research Scope and Objectives 

This RFA seeks to support studies that characterize tools, validate tools, or 
compare tools used in fMRI research.  Particularly welcomed are such studies 
of tools that are now widely used.  Information about such tools is likely to 
have a broad impact compared to information about tools used only in a few 
laboratories.

Also solicited is research and development of the means to characterize, 
validate, or compare these tools.  Such means might include the development of 
well-characterized data sets, metrics, etc, particularly welcomed are means to 
study tools with wide applicability for broad impact on the field.  It should 
be noted that the research proposed in response to this RFA may be driven by 
problems, design, or hypotheses.

General categories of research and development considered responsive to this 
RFA include:

o  Tool Characterization:  Understanding how the raw data are affected by data 
processing performed by informatics tools, which may include an understanding 
of the tool"s requirements, expectations, computational and data conditions 
under which it operates, etc.  Also considered responsive to this RFA are 
proposals to develop the means to carry out such characterization activities.

o  Tool Validation:  Studies to reveal whether a particular tool gives the 
answer it should give, and/or development of the means to conduct such 
studies.

o  Tool Comparison:  Studies to demonstrate which tool is best suited to 
perform which functions and under which conditions, etc., and/or development 
of the means to conduct such studies.

General categories of tools designed for functional activation studies that 
such research and development might focus on include:

o  Spatial normalization tools

o  Hemodynamic response models

o  Statistical analysis packages used widely in fMRI

o  Morphometric software packages

o  Data visualization tools

o  Segmentation and feature extraction software

o  Image processing tools (e.g., to correct field inhomogeneities, suppress 
noise, enhance contrast, equalize histograms, etc.)

To assure the greatest impact on neuroscience using fMRI, the tools studied 
should be in wide use by the fMRI neuroimaging research community.  Also, the 
means developed to study tools should be applicable to widely used tools.  In 
short, activities supported under this RFA should address significant 
practical problems and issues in the field.

SPECIAL REQUIREMENTS

The purpose of this RFA is to develop a body of scientific findings, and the 
means to produce such findings, that will likely have immediate impact on the 
research community using fMRI informatics tools.  Therefore, applications 
should include a plan that describes plans for making available to the 
research community the data, software, or other tools (e.g., a highly 
characterized data set) proposed to be developed with a grant funded under 
this RFA.  PHS policy requires that investigators make unique research 
resources readily available for research purposes to qualified individuals 
within the scientific community when they have been published (see PHS Grants 
Policy Statement revised March 1, 2001, at 
http://grants.nih.gov/grants/policy/nihgps_2001/index.htm.  The intent of this 
policy, however, is not to discourage, impede, or prohibit the organization 
that develops unique research resources or intellectual property from 
commercializing the products.

A detailed plan for how the data, software, or other tools will be made 
available to the research community broadly and in a timely way will be 
considered part of the scientific methodology for carrying out the research 
and, as such, the adequacy of the plan will be considered by reviewers in 
assessing merit.  This will also be considered by the program staff of 
participating Institutes in determining whether the grant will be awarded.  
This plan as approved, after negotiation with the applicant when necessary, 
will be a condition of the award.  The effectiveness of these efforts will 
also be considered in assessment of non-competitive renewals of the grant.

Finally, Principal Investigators funded under this RFA and appropriate staff 
chosen by them are expected to attend annual meetings convened by NIMH, NINDS, 
and NIBIB to discuss their progress.  Applicants, therefore, should include in 
their budget travel costs for this meeting each year.  The first of these 
meetings will take place soon after awards are made.

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

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

It is the policy of NIH 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 was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address:  http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning the policy.

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.  This policy announcement is found in the NIH Guide for Grants and 
Contracts Announcement dated June 5, 2000, at the following website: 
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

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.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an internet site.

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 give careful consideration to the issue of 
structuring informed consent statements and other human subjects procedures 
given the potential for wider use of data collected under this award.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, and telephone 
number of the Principal Investigator, the identities of other key personnel 
and participating institutions, and the number and title of the RFA in 
response to which the application may be submitted.  Although a letter of 
intent is not required, is not binding, and does not enter into the review of 
a subsequent application, the information that it contains allows IC staff to 
estimate the potential review workload and plan the review.

The letter of intent is to be sent to Dr. Michael F. Huerta at the address 
listed under INQUIRIES, by the letter of intent receipt date listed.

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html must be used in 
applying for these grants.  This version of the PHS 398 is available in an 
interactive, searchable format.  For further assistance contact GrantsInfo, 
Telephone 301/710-0267, Email:  [email protected].

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS 

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only when 
there is a possibility for an award. It is anticipated that these changes will 
reduce the administrative burden for the applicants, reviewers and NIH staff.  
The research grant application form PHS 398 (rev. 5/2001) at 
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in 
applying for these grants, with modular budget instructions provided in 
Section C of the application instructions.

The RFA label available in the PHS 398 (rev. 5/2001) 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.

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed, photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application with any 
appendix materials must be sent to:

Jean G. Noronha, Ph.D.
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD  20892-9609 

Applications must be received 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 (CSR) 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 addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
responsiveness by the participating Institutes.  Incomplete and/or non-
responsive applications will be returned to the applicant without further 
consideration.  Applications that are complete and responsive to the RFA will 
be evaluated for scientific and technical merit by an appropriate peer review 
group convened by the NIMH in accordance with the review criteria stated 
below.  As part of the initial merit review, all applications will receive a 
written critique and undergo a process in which only those applications deemed 
to have the highest scientific merit, generally the top half of the 
applications under review, will be discussed, assigned a priority score, and 
receive a second level review by the National Advisory Councils of the 
participating Institutes.

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 the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals.  Each of these 
criteria will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application.  Note that the 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, an 
investigator may propose to carry out important work that by its nature is not 
innovative but is essential to move a field forward.

(1) Significance:  Does this study address an important problem? If the aims 
of the application are achieved, how will scientific or technical knowledge be 
advanced?  What will be the effect of these studies on the concepts or methods 
that drive this field?  Will the information about tools or the means to study 
tools produced by these studies have broad impact on the research community 
that uses fMRI?

(2) Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?  Is the plan to make available to the research community 
data, software, or other tools developed in the application adequate?

(3) Innovation:  Does the project employ novel concepts, approaches or 
methods? Are the aims original and innovative?  Does the project challenge 
existing paradigms or develop new methodologies or technologies?

(4) Investigator:  Is the investigator appropriately trained and well suited 
to carry out this work?  Is the work proposed appropriate to the experience 
level of the principal investigator and other researchers (if any)?

(5) Environment:  Does the scientific environment in which the work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional 
support?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

o  The adequacy of plans to include both genders, minorities and their 
subgroups, and children as appropriate for the scientific goals of the 
research.  Plans for the recruitment and retention of subjects will also be 
evaluated.

o  The reasonableness of the proposed budget and duration in relation to the 
proposed research.

o  The adequacy of the proposed protection for humans, animals or the 
environment, to the extent they may be adversely affected by the project  
proposed in the application.

Schedule

Letter of Intent Receipt Date:    January 25, 2002
Application Receipt Date:         February 26, 2002
Peer Review Date:                 June 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

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or answer questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Michael F. Huerta, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7202, MSC 9645
Bethesda, MD  20892-9645
Rockville,  MD  20852 for express or courier service
Telephone:  (301) 443-3563  
FAX:  (301) 443-1731
Email:  [email protected]

Yuan Liu, Ph.D.
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 2110B
Bethesda, MD  20892-9523
Telephone:  (301) 496-3108
Email:  [email protected]

Richard E. Swaja, Ph.D.
Division of Biomedical Imaging
National Institute of Biomedical Imaging and Bioengineering
31 Center Drive, Room 1B37
Bethesda, MD  20892-2077
Telephone:  (301) 451-6771
FAX:  (301) 480-4515
Email:  [email protected]

Direct inquiries regarding fiscal matters to:

Ms. Carol J. Robinson
Grants Management Branch
National Institute of Mental Health
6001 Executive Boulevard, Room 6118, MSC 9605
Bethesda, MD  20892-9605
Telephone:  (301) 443-3858
FAX:  (301) 443-6885
Email:  [email protected]

Ms. Joellen Harper
Grants Management Branch
National Institute of Neurological Disorders and Stroke
6001 Executive Boulevard, Room 3258
Bethesda, MD  20892-9523
Telephone:  (301) 496-9231
Email:  [email protected]

Annette Hanopole, CRA
Grants Management Branch
National Institute of Biomedical Imaging and Bioengineering
31 Center Drive, Room 1B37  
Bethesda, MD  20892-2077
Telephone:  (301)451-6768
FAX:  (301) 480-4515
Email:  [email protected]

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.242 (NIMH), 93.853 (NINDS), and 93.286 (NIBIB).  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 and 
Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.  This program is not 
subject to the intergovernmental review requirements of Executive Order 12372 
or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-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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