SYSTEMS AND METHODS FOR SMALL ANIMAL IMAGING
RELEASE DATE: November 18, 2002
RFA: EB-03-002
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
(http://www.nibib.nih.gov)
LETTER OF INTENT RECEIPT DATE: January 16, 2003
APPLICATION RECEIPT DATE: February 13, 2003
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism(s) of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
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)
invites investigator-initiated applications for NIH Research Project
Grant (R01) awards to support interdisciplinary basic research or
Exploratory/Developmental Research (R21) awards to support novel
investigations related to the development of small animal imaging
devices and methods that can be applied broadly to research on diverse
biological or disease processes. A companion Program Announcement
related to this initiative is available at
(http://grants.nih.gov/grants/guide/pa-files/PA-03-031.html) for
those eligible for the Small Business Innovation Research/Small
Business Technology Transfer (SBIR/STTR) program.
The primary focus of this Request for Applications (RFA) is research
and development related to devices, methods, and imaging agents for the
investigation of biological and disease processes in small animals.
The integration of systems and methods with complementary imaging
and/or spectroscopy modalities is also included as appropriate to
provide anatomic, physiologic, metabolic, and molecular-level
information in small animal models of disease.
The motivation for this RFA is that recent discoveries in genomics and
molecular and cell biology have led to the development and wide use of
small animal models of human disease. One of the limitations with the
use of these models is the need to sacrifice large numbers of animals
for ex vivo tissue and molecular analysis. Imaging instrumentation and
methods that permit imaging on the scale of small animals offer an
opportunity to address this problem by enabling noninvasive
investigations of biological processes in vivo. This provides the
potential for longitudinal studies in the same animal. This coupling
of animal models of human disease with advances in imaging technology
presents an extraordinary opportunity for biomedical imaging to play an
important role in the early detection, diagnosis, and treatment of
disease. Several dedicated small animal imaging systems have been
developed and a few commercialized, although technological hurdles
still exist that limit the realization of the full potential of small
animal imaging for biomedical research and drug development. Progress
is needed to improve throughput, sensitivity, and spatial and temporal
resolution of small animal imaging devices, to provide quantitative
information through improved reconstruction methods that incorporate
models of physical effects, and to provide improved methods for system
validation. System optimization incorporating the design of molecular
probes that serve as links to particular biological processes in vivo
is also a focus. Further improvements in system design, image
processing and analysis software, and data sharing technology, coupled
with improvements and innovations in animal handling techniques used
during imaging, are needed to make small animal imaging technology more
accessible to molecular biologists and pharmaceutical scientists
desiring to use animal models as tools for biomedical research and drug
discovery and development.
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 the discovery and development of biomedical imaging
methods was identified at several NIH workshops and conferences on
biomedical imaging, including a June 25-26, 1999 symposium entitled
"Biomedical Imaging Symposium: Visualizing the Future of Biology and
Medicine" which was coordinated by the NIH Bioengineering Consortium
(BECON). Three scientific areas were addressed at the symposium: (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.
Additionally, small animal models of human disease, in particular mouse
models, have been identified as valuable resources for the
investigation of the underlying mechanisms of human disease. Small
animal imaging provides the means to address all three priority areas
through the non-invasive monitoring of biological processes, disease
progression, and response to therapy, with the potential to provide a
natural bridge to the clinical environment and contribute substantially
to the development of human medicine.
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 be accomplished effectively by multi-disciplinary teams
from academia, national laboratories, and industry, with expertise in
the quantitative, computational, and biomedical sciences. In addition,
the need 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 small animal imaging systems and
methods. Research areas of interest include the improvement of
existing devices and methods and the development of novel approaches to
small animal imaging that enhance spatial or temporal resolution,
measurement sensitivity, specificity, and throughput as required for
the detection, diagnosis, or measurement of treatment efficacy for
different disease processes. The scope of the RFA includes the
integration of molecular imaging systems and methods with anatomical or
other functional imaging and/or spectroscopy methods to provide more
effective tools for biomedical research. 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 is also a focus.
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 Development of small animal imaging systems that extend the
capabilities of existing devices through improved spatial and
temporal resolution, sensitivity, and throughput for screening
applications. This research scope includes improvements to dedicated
small animal imaging devices and adaptation of existing clinical
devices, in addition to high-risk, high-gain research objectives
such as new in vivo imaging and/or spectroscopy paradigms.
Development of multi-modality imaging approaches that increase the
range of information provided for enhanced image interpretation and
improved quantification of biological processes in vivo are also
within the scope of this RFA. Mathematical modeling of such systems
and their performance is included as required for system
optimization.
o Development of improved methods for image reconstruction and
processing, and the development of analytical tools for image
analysis. An emphasis of the RFA is on technological advances that
might enhance the capabilities of existing devices and increase the
availability of small animal imaging devices and methods for
biological research and drug discovery and development.
o Development of complementary devices and methods for improved animal
handling, including motion compensation and correction, imaging
agent administration, blood sampling, anesthesia delivery, and
animal maintenance and monitoring during imaging. Implantable sensor
devices that take advantage of microelectromechanical (MEMS) and
nanoelectromechanical (NEMS) systems are included.
o In vivo investigations of imaging agents and high-affinity molecular
probes for the imaging of biological processes in small animals,
including improved methods for probe delivery and targeting. These
studies may include the development of molecular probes for gene
expression, cell tracking, enzyme action or other metabolic
processes, or blood flow or drug distribution and action, with the
potential to impact the study of several disease processes. Single
or multiple imaging agents or multifunctional probes suitable for
multi-modality imaging and/or spectroscopy are included. System
optimization for imaging agents and molecular probes can be
addressed where appropriate. Studies involving in vitro
characterization of imaging agents and probes, and/or in vivo
testing in human subjects, are not within the scope of this RFA.
MECHANISM OF SUPPORT
This RFA will use NIH R01 (Research Project Grant) award mechanism and
the development/exploratory grant award mechanism (R21). As an
applicant you will be 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 2003.
The R01 mechanism is recommended for applications that emphasize basic
discovery or cross-cutting research that addresses specific aspects of
small animal imaging. Research periods associated with the R01
proposals are limited to five years.
The R21 Exploratory/Developmental Award supports exploratory or
developmental research aimed at proof-of-principle for high-risk
projects where no or very little preliminary data is available. An R21
application can be for up to two years with a maximum budget request of
$150,000 direct costs per year and a maximum page limit of 10 pages.
R21 applications are not renewable. If sufficient results are
generated during the term of the award, investigators are encouraged to
apply for further funding through the R01 mechanism (or other
appropriate mechanisms).
This RFA uses just-in-time concepts. It also uses 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 an application with direct costs in
each year of $250,000 or less, use the modular format. Otherwise
follow the instructions for non-modular research grant applications.
FUNDS AVAILABLE
The NIBIB intends to commit approximately $7,000,000 in FY 2003 to fund
20 to 30 new and/or competitive continuation grants in response to this
RFA. An applicant may request a project period of up to 5 years for an
R01 and a project period of up to 2 years for an R21. Budgets for
direct costs of up to $150,000 per year will be accepted for an R21.
There is no budget limitation for R01 applications.
Applications requesting up to $250,000 per year in direct costs must be
submitted in a modular grant format. Since the total costs for a
subcontract or consortium are included in the direct cost request, one
additional module of $25,000 may be requested for the facilities and
administrative costs associated with third party agreements. Under
these guidelines, R21 applications requesting $150,000 may request
$175,000 to cover the facilities and administrative costs described
above. A module requested for this purpose must be clearly identified
in the budget justification section of the application, and will be
restricted for this purpose only at the time of award.
Although the financial plans of the NIBIB provides 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.
ELIGIBLE INSTITUTIONS
You may submit (an) application(s) if your institution has any of the
following characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges,
hospitals, and 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
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH programs.
SPECIAL REQUIREMENTS
General Clinical Research Centers:
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources
(NCRR) may wish to identify the GCRC as a resource for conducting the
proposed research. If so, a letter of agreement from either the GCRC
program director or principal investigator should be included with the
application.
Meetings:
Principal Investigators will be required to attend an annual meeting
organized by NIBIB. Please include travel to the Bethesda, MD area as
part of the budget request.
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 or grants
management issues:
o Direct questions about scientific/research issues related to the
NIBIB to:
Brenda Korte, Ph.D.
Division of Biomedical Imaging
National Institute of Biomedical Imaging and Bioengineering
NIH/DHHS
6707 Democracy Boulevard – Suite 200
Bethesda, MD 20892-5469
Telephone: 301-451-4774
Fax: 301-480-4973
Email: kortebr@nibib.nih.gov
The National Institute of Mental Health, while not a sponsor of this
program announcement, supports research and development similar to that
solicited here, with particular interest in such projects relevant to
brain research. Dr. Michael Huerta (mhuerta@helix.nih.gov, 301-443-
3563) is an appropriate contact at NIMH for such research interests.
o Direct questions about peer review issues to:
David T. George, Ph.D.
Chief, Office of Scientific Review
National Institute of Biomedical Imaging and Bioengineering
NIH/DHHS
6707 Democracy Blvd., Suite 920
Bethesda, MD 20892-5469
Telephone: 301-451-4772
Fax: 301-480-4973
Email: dg174c@nih.gov
o Direct questions about NIBIB financial management or grants
management matters to:
Ms. Florence Turska
Grants Management Officer
National Institute of Biomedical Imaging and Bioengineering
NIH/DHHS
6707 Democracy Boulevard – Suite 900
Bethesda, MD 20892-5469
Telephone: 301-496-9314
Fax: 301-480-4974
Email: turskaf@nibib.nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
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 by the date listed at the beginning
of this document. The letter of intent should be sent to David T.
George, Ph.D. at the address listed under WHERE TO SEND INQUIRIES.
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant
application instructions and forms (rev. 5/2001). The PHS 398 is
available at http://grants.nih.gov/grants/funding/phs398/phs398.html in
an interactive format. For further assistance contact GrantsInfo,
Telephone (301) 435-0714, Email: 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) 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) 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.
SENDING AN APPLICATION TO THE NIH: 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 and
all five collated sets of Appendix material must be sent to Dr. David
T. George at the address listed under WHERE TO SEND INQUIRIES.
APPLICATION PROCESSING: 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.
Principal investigators should not send supplementary material without
first contacting the Scientific Review Administrator (SRA). The SRA
will be identified in the letter sent to you indicating that your
application has been received. If you have not received such a letter
within three weeks after submitting the application, contact Dr. David
George at the address listed under WHERE TO SEND INQUIRIES.
Please Note: As of November 27, 2001, all applications and other
deliveries to the Center for Scientific Review must come via courier
delivery or the USPS. Applications delivered by individuals to the
Center for Scientific Review will no longer be accepted. For
additional information, see the NIH Guide Notice
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-012.html.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and for responsiveness by the NIBIB. Incomplete applications will be
returned to the applicant without further consideration. If the
application is not responsive to the RFA, NIBIB staff may contact the
applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next appropriate NIH review cycle.
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 NIBIB in accordance with the review
criteria stated below. As part of the initial merit review, all
applications will:
o Receive a written critique
o 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 and assigned a priority score
o Receive a second level review by the National Advisory Council for
Biomedical Imaging and Bioengineering.
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 in order 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 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 propose to carry out important work that by its nature is not
innovative but is essential to move a field forward.
(1) SIGNIFICANCE: Does your study address an important problem? If the
aims of your application are achieved, how do they advance scientific
knowledge? What will be the effect of these studies on the concepts or
methods that drive this field?
(2) APPROACH: Are the conceptual framework, design, methods, and
analyses adequately developed, well integrated, and appropriate to the
aims of the project? Do you acknowledge potential problem areas and
consider alternative tactics?
(3) INNOVATION: Does your project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does your project
challenge existing paradigms or develop new methodologies or
technologies?
(4) INVESTIGATOR: Are you appropriately trained and well suited to
carry out this work? Is the work proposed appropriate to your
experience level as the principal investigator and to that of other
researchers (if any)?
(5) ENVIRONMENT: Does the scientific environment in which your 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?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, your
application will also be reviewed with respect to the following:
o R21 MECHANISM ONLY: Since the R21 mechanism is intended to encourage
exploratory/developmental research, proposals submitted as an R21 will
also be reviewed based on their high risk/high impact potential and
whether or not the proposal is significantly distinct from those
traditionally submitted through the R01 mechanism.
o PROTECTIONS: 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.
o INCLUSION: The adequacy of plans to include subjects from both
genders, all racial and ethnic groups (and subgroups), and children as
appropriate for the scientific goals of the research. Plans for the
recruitment and retention of subjects will also be evaluated. (See
Inclusion Criteria included in the section on Federal Citations, below)
o DATA SHARING: The adequacy of the proposed plan to share data.
o BUDGET: The reasonableness of the proposed budget and the requested
period of support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: January 16, 2003
Application Receipt Date: February 13, 2003
Peer Review Date: June/July 2003
Council Review: September 2003
Earliest Anticipated Start Date: September 30, 2003
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
HUMAN EMBRYONIC STEM CELLS (hESC): Criteria for federal funding of
research on hESCs can be found at
http://grants.nih.gov/grants/stem_cells.htm and at
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html.
Only research using hESC lines that are registered in the NIH Human
Embryonic Stem Cell Registry will be eligible for Federal funding (see
http://escr.nih.gov). It is the responsibility of the applicant to
provide the official NIH identifier(s)for the hESC line(s)to be used in
the proposed research. Applications that do not provide this
information will be returned without review.
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: This program is described in the Catalog of
Federal Domestic Assistance No. 93.286 and 93.287 and is 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.
Return to Volume Index
Return to NIH Guide Main Index