Full Text HL-93-07


NIH GUIDE, Volume 21, Number 44, December 11, 1992

RFA:  HL-93-07-H

P.T. 34

  Medical/Diagnostic Imaging 
  Cardiovascular System 

National Heart, Lung, and Blood Institute

Letter of Intent Receipt Date:  July 5, 1993
Application Receipt Date:  October 13, 1993


This solicitation will support grants for research and development of
monoenergetic and/or nearly monoenergetic x-ray sources that can be
hospital based and clinically applicable for imaging cardiovascular
structures.  It is desirable that the proposed imaging system be
tuneable so as to achieve spectral concentration in a single line or
very narrow band to deliver energy in a band and at an intensity
appropriate for specific cardiovascular imaging applications.


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), Monoenergetic X-ray Systems for Cardiovascular
Imaging, is related to the priority area of cardiovascular imaging.
Potential applicants may obtain a copy of "Healthy People 2000" (Full
Report:  Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary
Report:  Stock No. 017-002-00473-1) through the Superintendent of
Documents, Government Printing Office, Washington, DC 20402-9325
(telephone 202-783-3238).


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.  Federal
agencies must also ensure that their own authorizing legislation will
allow them to respond to this solicitation and to receive a PHS grant.
Applications from minority individuals and women are encouraged.


This RFA will use the National Institutes of Health (NIH) individual
research grant (R01).  Responsibility for the planning, direction, and
execution of the proposed project will be solely that of the applicant.
The total project period for applications submitted in response to the
present RFA may not exceed five 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 April 1, 1994.  Because the nature and scope
of the research proposed in response to this RFA may vary, it is
anticipated that the size of an award will vary also.


Approximately $1.5 million in total costs will be provided for the
first year of support for the entire program.  It is anticipated that
three to four new grants will be awarded under this program.  This
level of support is dependent on the receipt of a sufficient number of
applications of high scientific merit.  Although this program is
provided for in the financial plan of the National Heart, Lung, and
Blood Institute (NHLBI), awards pursuant to this RFA are contigent upon
the availability of funds for this purpose. Administrative adjustments
in project period and/or amount of support may be required at the time
of the award.



Biomedical imaging with x-ray systems continues to be widely used.
Despite exposing subjects to undesirable ionizing radiation, the
resolution and image quality obtained with x-ray systems surpasses
other imaging modalities for many applications.  In a number of
instances, however, the benefits of repeated x-ray procedures are
offset by the risks of exposure.  Examples are angiography,
mammography, and fluoroscopy during ablation of cardiac conduction
tissue, especially for children.  A new type of x-ray source with
characteristics that reduce exposure but maintain or improve image
quality would provide broad biomedical benefits.  A monoenergetic or
nearly monoenergetic x-ray source with certain special characteristics
is desirable, e.g., spectral concentration, high brightness, tunable,
and highly directional and polarized.

An x-ray source with a narrow frequency range, ideally at a single
frequency, would be advantageous because it would allow x-rays only at
the desired frequency to be produced, eliminating radiation outside of
the spectrum necessary for imaging.  In angiography, for example, an
iodinated agent is injected into the arterial system to provide
contrast.  The attenuation of x-rays by iodine changes by orders of
magnitude for x-rays just below approximately 33.2 kiloelectron volts
(keV) as compared with x-rays just above 33.2 keV.
By eliminating x-ray frequencies outside of the range required for a
specific application, the dose may be significantly reduced.  It has
been estimated that mammographic examinations performed with near
monoenergetic x-rays will deliver a dose to the patient that will be
from one-tenth to one-fiftieth as much as the dose delivered with a
conventional x-ray system.  This estimate is similarly applicable to
angiography studies.

Over the past nine years, the NHLBI has been supporting research in
energy subtraction imaging with monoenergetic radiation generated from
the synchrotron source at Stanford University.  In the original design,
two images bracketing 33.2 keV were required to be obtained
sequentially before subtracting them, which is the way this is
accomplished with conventional x-ray sources.  An innovation developed
at Stanford is the use of two detectors, allowing simultaneous image
acquisition before subtraction, thus effectively eliminating effects of
patient motion, an important concept for coronary artery visualization.
Using the synchrotron facility at Brookhaven National Laboratory,
images of coronary arteries have now been obtained, but only at an
experimental level.  The crystal monochromatization required for
detection entails a significant diminution in beam intensity.  Further,
a synchrotron is very costly and limits the accessibility of the

Other issues

Several processes for producing monoenergetic x-rays without the need
for a large, expensive linear accelerator such as a synchrotron have
been reported, all of which require that relativistic electrons be
produced, i.e., electrons traveling at nearly the speed of light.  Most
of these processes have been theoretically described and some have been
demonstrated experimentally.  Channeling radiation, transition
radiation, parametric conversion, and free electron laser production
are examples of such processes.  Although each of these processes
requires that electrons be accelerated to near the speed of light, a
synchrotron or similar very large and expensive linear accelerator may
not be needed.  A major goal of this solicitation is to demonstrate
whether or not monoenergetic x-rays can be produced with a clinically
applicable, hospital based system.

This RFA seeks to support grant applications to study, develop and
evaluate minimally invasive x-ray systems using monoenergetic radiation
to achieve improved resolution and image quality.  Complete systems
would need to be described, including both source and detector.  Grant
applications should propose a specific application, such as coronary
artery imaging without intraarterial injection of contrast material,
and include quantitative objectives for resolution, patient dose, and
image quality.  Grant applications should also emphasize close
collaboration among physicists, biophysicists, radiologists,
cardiologists, and engineers with both a theoretical basis and an
experimental plan for the proposed system.

Proposed Research

Grant applications may propose research in imaging systems for
cardiovascular application utilizing tuneable monoenergetic x-ray
sources and detector systems to deliver energy at appropriate
intensities, including, but not limited to, the following technologies:

o  Transition x-ray sources

o  Channeling radiation sources

o  Cerenkov radiation sources

o  Smith-Purcell radiation sources

o  Parametric conversion systems

o  Coherent superlattice radiation systems

It is desirable that each application provide evidence that the
proposed system is feasible as a hospital based facility, with size and
cost estimates based upon calculations and experimental data.


Awardees will be requested to meet twice annually to exchange
information and to report on progress, including coordination of
activities in appropriate areas.  Applicants are advised to include
such plans in their budget requests, including their willingness to
participate in such activities.


NIH policy is that applicants for NIH clinical research grants and
cooperative agreements are required to include minorities and women in
study populations so that research findings can be of benefit to all
persons at risk of the disease, disorder or condition under study;
special emphasis must be placed on the need for inclusion of minorities
and women in studies of diseases, disorders and conditions which
disproportionately affect them.  This policy is intended to apply to
males and females of all ages.  If women or minorities are excluded or
inadequately represented in clinical research, particularly in proposed
population-based studies, a clear compelling rationale must be

The composition of the proposed study population must be described in
terms of gender and racial/ethnic group.  In addition, gender and
racial/ethnic issues must be addressed in developing a research design
and sample size appropriate for the scientific objectives of the study.
This information must be included in the form PHS 398 (rev. 9/91) in
Sections 1-4 of the Research Plan AND summarized in Section 5, Human
Subjects.  Applicants are urged to assess carefully the feasibility of
including adequate numbers of women.

For the purpose of this policy, clinical research is defined as human
biomedical and behavioral studies of etiology, epidemiology, prevention
(and preventive strategies, diagnosis, or treatment of diseases,
disorders or conditions, including, but not limited to, clinical

The usual NIH policies concerning research on human subjects also
apply.  Basic research or clinical studies in which human tissues
cannot be identified or linked to individuals are excluded.  However,
every effort should be made to include human tissues from women and
racial/ethnic minorities when it is important to apply the results of
the study broadly, and this should be addressed by applicants.

For foreign awards, the policy on inclusion of women applies fully;
since the definition of minority differs in other countries, the
applicant must discuss the relevance of research involving foreign
population groups to the United States populations, including

If the required information is not contained within the application,
the application will not be accepted for review.

Peer reviewers will address specifically whether the research plan in
the application conforms to these policies.  If the representation of
women or minorities in a study design is inadequate to answer the
scientific question(s) addressed AND the justification for the selected
study population is inadequate, it will be considered a scientific
weakness or deficiency in the study design and reflected in assigning
the priority score to the application.

All applications for clinical research submitted to NIH are required to
address these policies. NIH funding components will not award grants or
cooperative agreements that do not comply with these policies.


Prospective applicants are asked to submit, by July 5, 1993, 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 subsequent applications, the information
that it contains allows NHLBI staff to estimate the potential review
workload and to avoid conflict of interest in the review.

The letter of intent is to be sent to:

Chief, Centers and Special Projects Section
Review Branch, Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 553A
Bethesda, MD  20892
Telephone:  (301) 496-7351
FAX:  (301) 402-1660


The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research and from the Office of
Grants Inquiries, Division of Research Grants, National Institutes of
Health, Westwood Building, Room 449, Bethesda, MD  20892, telephone
(301) 496 7441.

The RFA label available in the 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, to
identify the application as a response to this RFA, check "YES", enter
the title Monoenergetic X-Ray Systems for Cardiovascular Imaging, and
the RFA number HL-93-07-H on line 2a of the face page of the

Send or deliver a signed, typewritten original of the application,
including the Checklist, and three signed photocopies to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

Send two additional copies of the application to the Chief, Centers and
Special Projects Section, at the address listed under LETTER OF INTENT.
It is important to send these two copies at the same time as the
original and three copies are sent to the Division of Research Grants
(DRG), otherwise the NHLBI cannot guarantee the the application will be
reviewed in competition for this RFA.

Applications must be received by October 13, 1993.  If an application
is received after that date, it will be returned to the applicant
without review.  The DRG will not accept any application in response to
this announcement that is essentially the same as one currently pending
initial review, unless the applicant withdraws the pending application.
The DRG 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


Upon receipt, applications will be reviewed by the DRG staff for
completeness and by the NHLBI for responsiveness.  Incomplete
applications will be returned to the applicant without further
consideration.  If the application is not responsive to the RFA, NHLBI
staff will 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 review cycle.

Applications may be triaged by an NHLBI peer review group on the basis
of relative competitiveness.  The NIH will withdraw from further
competition those applications judged to be non-competitive for award
and notify the applicant Principal Investigator and institutional
official.  Those applications judged to be competitive will undergo
further scientific merit review.  Those applications that are complete
and responsive will be evaluated in accordance with the criteria stated
below for scientific/technical merit by an appropriate peer review
group convened by the NHLBI.  The second level of review will be
provided by the National Heart, Lung and Blood Advisory Council.

Review criteria for RFAs are generally the same as those for
unsolicited research grant applications.

o  the novelty, originality and feasibility of the approach and the
adequacy of the experimental design

o  the competence of the principal investigator and collaborators to
accomplish the proposed research, and the commitment and time they will
devote to the project

o  the suitability of the facilities to perform the proposed research,
including laboratories, instrumentation, and data management systems

o  the appropriateness of the requested budget and duration for the
proposed research

o  adequate plans for interaction and communication of information and
concepts among investigators involved in collaborative studies


Although multidisciplinary approaches are encouraged, it is not the
intent of this announcement to solicit applications for large studies
that would encompass a variety of independent projects, i.e., program
projects.  This program will not support clinical trials or large
epidemiological studies.  In general, funds will not be provided for
the purchase and installation of expensive, new equipment.  Awards
under this announcement to foreign institutions will be made only for
research of very unusual merit, need and promise, and in accordance
with PHS policy governing such awards.

Upon initiation of the program, the Division of Heart and Vascular
Diseases will sponsor periodic meetings to encourage exchange of
information among investigators who participate in this program, and to
stimulate collaboration.


Inquiries regarding this announcement may be directed to:

Dr. Alan Berson or Dr. Rosalie Dunn
Devices and Technology Branch
Division of Heart and Vascular Diseases
National Heart, Lung and Blood Institute
Federal Building, Room 312
Bethesda, MD  20892
Telephone:  (301) 496-1586

Direct inquiries regarding fiscal and administrative matters to:

Mr. William Darby
Grants Operations Branch
Division of Extramural Affairs
National Heart, Lung and Blood Institute
Westwood Building, Room 4A11
Bethesda, MD  20892
Telephone:  (301) 496-7536
FAX:  (301) 402-1200


This program is described in the Catalog of Federal Domestic Assistance
No. 93.837., Heart and Vascular Diseases.  Awards will be made under
the authority of the Public Health Service Act, Section 301 (42 USC
241) and administered under PHS grants policies and Federal
Regulations, most specifically 42 CFR Part 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.


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