Release Date:  March 25, 1998

RFA:  HD-98-006


National Institute of Child Health and Human Development
National Institute of Arthritis and Musculoskeletal and Skin Diseases

Letter of Intent Receipt Date:  May 20, 1998
Application Receipt Date:  July 24, 1998


The National Center for Medical Rehabilitation Research (NCMRR) of the National
Institute of Child Health and Human Development (NICHD) and the National
Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) invite
applications for research that employs contemporary imaging methods to:  (1)
analyze mechanisms of soft tissue injury and repair in relation to the
functioning of the extremities; (2) develop computer-based models to quantify the
biomechanical environment and function of soft tissues of the extremities; or (3)
document the outcomes of treatment interventions aimed at facilitating soft
tissue repair and promoting functioning of the extremities.  The major goal of
this initiative is to better understand the recovery of soft tissue integrity and
functioning of the extremities of individuals with disabling soft tissue


The Public Health Service (PHS) is committed to achieving the health promotion
and disease prevention objectives of "Healthy People 2000," a PHS-led national
activity for setting priority areas.  This Request for Applications (RFA),
"Imaging in Medical Rehabilitation," is related to the priority area of chronic
and disabling conditions and the goal to reduce health disparities among
Americans.  Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report: Stock No. 017-001-00474-0 or Summary Report: Stock No. 017-001-00473-1)
through the Superintendent of Documents, Government Printing office, Washington,
DC 20402-9325 (telephone 202-512-1800).


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.


This program will use the National Institutes of Health (NIH) individual research
project grant (R01).  Responsibility for the planning, direction, and execution
of the proposed project will be solely that of the applicant.  The total (direct
and indirect) costs for any application in any one-year budget period may not
exceed $260,000.  The anticipated award date is April 1, 1999.

This RFA is a one-time solicitation.  Future unsolicited competing continuation
applications will compete with all unsolicited investigator-initiated
applications and will be reviewed according to the customary peer review


Approximately $1,500,000 in total costs for FY 99 will be committed to fund
applications that are submitted in response to this RFA.  NICHD will allocate
approximately $1,000,000 in total costs for FY 99 to support four to six awards. 
NIAMS will allocate approximately $500,000 in total costs for FY 99 to support
two to three awards.  The number of awards depends on the overall scientific
merit of the applications, their relevance to the stated goals of this RFA, and
the availability of funds.



Soft tissue injuries in the extremities are among the leading causes of activity
limitations, restrictions during sports/recreational activities, and losses of
time at work and school.  The integrity of soft tissues such as muscles, tendons,
ligaments, and cartilage is important for maintaining joint stability, decreasing
susceptibility to other injuries, and preventing the development of degenerative
joint disease.  It is essential to have a better understanding of how the
structure and functioning of such tissues are affected by injury or degenerative
conditions and how repair processes can be facilitated.  These areas offer the
potential for fruitful collaborations between clinicians and basic researchers.

On a daily basis, health care providers encounter clinical phenomena that are
clearly important, but not well understood in biological terms.  A large number
of these soft tissue injuries involve the soft tissues of the hands, arms, feet,
and legs.  Limited capabilities of visualization and quantification have hampered
the detailed study of  repair processes and the recovery of functioning of
impaired extremities.  Modern imaging technology has much to contribute to
elucidating these processes, developing more effective treatments, and evaluating
their outcomes.


Applications should focus on the soft tissue repair and functioning of the
extremities, studied by means of contemporary imaging methods, e.g., x-ray
projection imaging, x-ray computed tomography, magnetic resonance imaging,
magnetic resonance spectroscopy, single photon tomography, positron emission
tomography, ultrasound imaging, electrical source imaging, electrical impedance
tomography, magnetic source imaging or medical optical imaging.  Applications
must address one or more of the following research themes.

I. Mechanisms of soft tissue repair

Research will be supported that analyzes repair mechanisms in the soft tissues
of the extremities (e.g., muscles, tendons, ligaments, cartilage, bursae, and
fasciae) of individuals with acute/chronic injuries.  The research may focus on
the relationship of soft tissue pathology to impairments (e.g., diminished range
of motion or muscle strength) or to functional limitations (e.g., ambulation or
self-care activities).  Emphasis should be placed on understanding how
pathophysiological changes in the structure and processes of soft tissues impact
on the limbs' functional capabilities and on individuals' use of their limbs to
perform activities of daily living or other desired activities.

Illustrative of appropriate research are studies that use imaging methods to
document age or gender differences in the biochemistry of injury responses and
soft tissue repair following trauma.  Also relevant are studies that use imaging
data to describe the effects of (a) limb disuse or soft tissue atrophy in people
with conditions such as stroke, or (b) spasticity on the development of
contractures in people with congenital conditions such as cerebral palsy, or (c)
imaging data to better understand the pathophysiology and repair of overuse

II. Model development

Detailed understanding is lacking of how the structure and functioning of the
soft tissue of the extremities are affected by injury, or by degenerative
conditions such as muscular dystrophy.  The development of computer graphic
models based on imaging data is promising for clarifying these issues and for
illuminating how repair processes proceed in the functional recovery of the
extremities.  Modeling may also advance understanding of repair processes that
are enhanced by treatment interventions such as physical therapy or surgery.  For
example, models might be developed to analyze the effects of tendon transfers to
reduce the spasticity that is associated with cerebral palsy, or for
investigating the effects of repetitive use of muscles, tendons, ligaments, and

III. Interventions

Research is encouraged that explores the usefulness of contemporary imaging
techniques to document the outcomes of treatment interventions such as surgery,
physical therapy, drug therapy, or functional electrical stimulation on the
recovery of limb function.  For example, it is generally recognized that
contractures can form in the immobilized or spastic limb that limit range of
motion and function.  Preventive or therapeutic treatments of contractures often
use the application of forces, motions, or physical modalities such as heat and
electrical stimulation on soft tissues.   Notwithstanding their therapeutic
potential, these interventions are also capable of interfering with healing or
of producing secondary injury such as repetitive microtrauma.  Studies are needed
of how these interventions can be optimized in order to maintain tissue
integrity, promote healing, and restore useful limb functioning.   As another
example, imaging techniques might be used to monitor the contribution of various
growth factors promoting the healing or functional enhancement of soft tissues
in the extremities.

Applicants are encouraged to communicate with program staff regarding the
responsiveness of other topics to this RFA.


National Institute of Child Health and Human Development (1993). Research Plan
for the National Center for the National Center for Medical Rehabilitation
Research. Bethesda, MD: DHHS, PHS, NIH, NICHD, Pub. No. 93-3509.

Research on Repetitive Motion Disorders" (PA-97-059), in the NIH Guide, Volume
26, Number 16, May, 1997.


It is the policy of the NIH that women and members of minority groups and their
subpopulations must be included in all NIH supported biomedical and behavioral
research projects involving human subjects, unless a clear and compelling
rationale and 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 research involving human subjects should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical
Research," which have been published in the Federal Register of March 28, 1994
(59 FR 14508-14513) and the NIH Guide for Grants and Contracts, Volume 23, Number
11, March 18, 1994.


Prospective applicants are asked to submit, by May 20, 1998, 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 is being 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 program and
review staff to estimate the potential review workload and avoid conflict of
interest in the review.

This letter of intent is to be sent to:

Louis A. Quatrano, Ph.D.
National Center for Medical Rehabilitation Research
National Institute of Child Health and Human Development
Building 61E, Room 2AO3
Bethesda, MD  20892-7510
Telephone:  (301) 402-2242
FAX:  (301) 402-0832


The research grant application form PHS 398 (rev. 5/95) is to be used in applying
for these grants.  These forms are available at most institutional offices of
sponsored research; from the Division of Extramural Outreach and Information
Resources, National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone 301/710-0267, Email:  The
PHS 398 may also be downloaded over the Internet from

The RFA label available in the PHS 398 (rev. 5/95) application form must be
affixed to the bottom of the face page of the application.  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.

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

BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier services)

At the time of submission, two additional copies of the application must be sent

Scott F, Andres, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
Building 6100, Room 5E03H
6100 Executive Boulevard
Bethesda, MD 20892-7510
Rockville, MD 20852 (for express/courier service)

Applications must be received by July 24, 1998.  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 previously 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.


Upon receipt, applications will be reviewed for completeness by CSR and for
responsiveness by staff at the NICHD and the NIAMS.  Incomplete applications will
be returned to the applicant without further consideration.  If the application
is not responsive to the RFA, NICHD staff may contact the applicant to determine
whether to return the application or submit it for review in competition with
unsolicited applications at the next 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 NICHD in accordance
with the review criteria stated below.

As part of the initial merit review, a process may be used in which  applications
will be determined to be competitive or noncompetitive based on their scientific
merit relative to other applications received in response to the RFA. 
Applications judged to be competitive will be discussed and assigned a priority
score.  Applications determined to be noncompetitive will be withdrawn from
further consideration and the principal investigator will be sent a summary
statement presenting the reviewers' comments.

Review Criteria

The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.  The
reviewers will comment on the following aspects of the application in their
written critiques 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 by the reviewers 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 a 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 knowledge be advanced?  What
will be the effect of these studies on the concepts or methods that drive this

(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?

(3) Innovation:  Does the project employ novel concepts, approaches or method?
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
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.


Applications will be selected for funding based on scientific merit of the
proposal, the availability of funds, and program priorities.


Inquiries are encouraged.  The opportunity to clarify any issues or questions
from potential applicants is welcomed.  Additional information on the National
Center for Medical Rehabilitation Research is available on the Web  at

Direct inquiries regarding programmatic issues to:

Louis A. Quatrano, Ph.D.
National Center for Medical Rehabilitation Research
National Institute of Child Health and Human Development
Building 61E, Room 2AO3
Bethesda, MD  20892-7510
Telephone:  (301) 402-2242
FAX:  (301) 402-0832

James S. Panagis, M.D., M.P.H.
Orthopaedics Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-37K, MSC 4500
Bethesda, MD  20892-6500
Telephone:  (301) 594-5055
FAX:  (301) 480-4543

Richard W. Lymn, Ph.D.
Muscle Biology Program
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-49E, MSC 4500
Bethesda, MD  20892-6500
Telephone:  (301) 594-5128
FAX:  (301) 480-4543

Direct inquiries regarding fiscal matters to:

Mary Ellen Colvin
Grants Management Branch
National Institute of Child Health and Human Development
Building 61E, Room 8A17
Bethesda, MD  20892-7510
Telephone:  (301) 496-1303
Fax: (301) 402-0915

Ms. Sally A. Nichols
Grants Management Office
National Institute of Arthritis and Musculoskeletal and Skin Diseases
45 Center Drive, Room 5AS-49F, MSC 4500
Bethesda, MD  20892-6500
Telephone:  (301) 594-3535
FAX:  (301) 480-5450


This program is described in the Catalog of Federal Domestic Assistance No.
93.929 Medical Rehabilitation Research and No. 93.846 Arthritis, Musculoskeletal
and Skin Diseases Research.  Awards are made under authorization of the Public
Health Service Act, Title IV, Part A (Public Law 78-410, as amended by Public Law
99-158, 42 USC 241 and 285) and administered under PHS grants policies and
Federal Regulations 42 CFR 52 and 45 CFR Part 74.  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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