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National Institutes of Health (U.S.). Division of.

Annual report : National Institutes of Health. Division of Research Grants (Volume 1979) online

. (page 18 of 24)
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will be tried. The electrochemical method of measuring mass transfer
coefficients will be used in several model systems. In the preliminary
phases of this work, the following techniques have been used.

^1) Dye injection . At selected sites in the arterial model, small
ports are drilled for insertion of #30 gauze hypodermic tubinq, which
is connected via PE 10 catheter tubing to a reservoir of colored dye.
The end of the hypodermic tubing can be positioned at any radial location
in the flow model and the dye slowly injected into the flow to mark
the streamlines. The streamline patterns at several sites can then
be recorded using 35~mm still photography. Initial data obtained by
dye injection into the flow indicates that the flow streamlines are'
skewed toward the side-arm branches exiting from the main faortic) flow
channel and that unusual patterns of hackflow and secondary flow occur
near the channel wall just opposite the branch orifices.

(2) Hydrogen bubble technique . At selected sites in the arterial model,
small grooves are milled into the model for the installation of 3-mil
stainless steel wire. Several wires run across the diameter of the

flow channel at locations in both the main branch and the side branches.
The wires serve as cathodes in a system consisting of a remote anode
and an electrolytic solution of sodium chloride. By pulsing a DC current
through the system, hydrogen bubbles are evolved all along the cathode
wire, which are in turn sweot away by the flow. In such a manner, each
element of fluid passing the wire is marked by the visible hydrogen
bubbles and the shape of the velocity profiles can be recorded with
appropriate photography,

(3) Neutrally buoyant microspheres . This method employs a dilute suspen-
sion of 100- to 500-micron diameter polystyrene microspheres in a 20

to 25 percent glycerine/water solution, which serves as the test fluid
in the flow model. The microspheres are dyed with a fluorescent dye
and then illuminated with ultraviolet light making them clearly visible
in the flow system. The oath of the microspheres can be photographed
with high-speed cinematography as these neutrally buoyant particles
move along with the fluid. In such a manner, the direction and velocity
of fluid elements can be determined.



45



ZOl RS 10041-02 BE!

(4) Laser Doppler velocimetry . When light is scattered from a moving
object, a stationary observer will see a change in the frequency of
the scattered light (Doppler shift) proportional to the velocity of
the object. This Doppler shift is used to measure the velocity of oart-
icles at various locations in the fluid. From the particle velocity,
the fluid velocity is inferred. A laser is used as the light source
because it is easily focused and coherent. This method allows us to
determine, quantitatively, the velocity profiles at various positions
in the arterial model.

Significance : Elucidation of the role of hemodynamics on the onset
and develooment of atherosclerotic plaques is fundamental in the study
of vascular disease. Certain biological evidence suggest that areas
of increased plaque formation may correlate with areas frequently exposed
to disturbed flow, for example, flow separation, or to relatively stable
flow patterns that change direction and magnitude periodically through-
out the day with varying metabolic and blood flow demands. This study
should demonstrate various types of flow patterns that can occur in
arterial systems as a function of changing flow parameters. Likewise,
the mass transfer of blood borne constituents like oxygen or lipopro-
teins can be affected by the flow patterns in various regions near the
artery wall. An imbalance in the mass transfer of these elements can
cause either vascular damage or excess accumulation of lipids which
can eventually lead to a pathological state in the artery wall.

Proposed Course : (1) Design and fabricate arterial models. (2) Study
the flow patterns in these models using the various techniques described
above as a function of several flow parameters such as Reynolds number,
branch flow ratio, and flow pulse frequency. (3) Correlate these findings
with those of our previous experiments on wall shear stress in similar
models. (4) Determine the mass transfer coefficients to the arterial
wall as a function of various Schmidt numbers under conditions of steady
and pulsatile flow. (5) Correlate all hemodynamic evidence with inci-
dence of lesions in experimental animals.



46



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Oo NOT use this space)



U.S. DEPARTMENT OF
HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RS 10042-02 BEI



PERIOD COVERED



nrt.nhpr 1, 1 Q7R t.n Spnt.PmhPr ?n, iq7Q

TITLE OF PROJECT (80 characters or less) '



The Use of Microprocessor-Based "Intelligent" Machines in Patient Care



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI:
OTHER:



M. Eden Chief BEIB DRS

H. Eden Assistant to the Chief BEIB DRS

P. Bungay Chemical Engineer BEIB DRS

W. Friauf Chief EEES BEIB DRS

B. McLees Chief DCCM CC
K. Kempner Electronics Engineer CSL DCRT
R. Martino Electronics Engineer CSL DCRT
R. Branson Georgetown University

N. DeClaris University of Maryland

T. Field Franklin Pierce lavi Center

M. Frankel Wayne State University

C. Soiegel George Washington University
A. Teich Technoscience Associates



COOPERATING UNITS ( i iK^n jWameT University of Michigan
Georgetown University; University of Maryland; Franklin Pierce Law Center;
Wayne State University; George Washington University; Technoscience
Associates; University of Michigan

lab/branch ' '



Biomedical Engineering and Instrumentation



SECTION

Office of the Chief



INSTITUTE AND LOCATION ' "

DRS. NIH. Bethesda. Maryland 20205



TOTAL MANYEARS:



0.5



PROFESSIONAL:



CHECK APPROPRIATE BOX(ES)
D (a) HUMAN SUBJECTS

D (al) MINORS □ (a2) INTERVIEWS



0.5



OTHER:



D (b) HUMAN TISSUES



(c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords) ~ '

As part of NIH's overall Consensus Development effort, BEIB is planning
to host a conference on "The Use of Microprocessor-Based 'Intelligent'
Machines in Patient Care" on October 17-19 in the Washington, D.C. area.
The branch will provide conference participants with a set of introduc-
tory working papers which arose out of four planning workshops in 1978.
The participants to the upcoming conference will seek agreement on social
and technical issues underlying the development of medical systems which
contain microprocessors.



PHS-604Q
(Rev. 10-76)



47



ZOl RS 10042-02 BEI



Objectives : To identify, clarify, and preliminarily assess the technical
and social issues underlying the development of microprocessor-based
"intelligent" machines for patient care - especially as they relate to
systems capable of autonomously adjusting treatment of patients.

Methods Employed : NIH and non-NIH members of the academic community
are meeting in an open conference in an attempt to reach a consensus
on (1) the technology's current state-of-the-art, (2) its prospects
for future development, and (3) a oreliminary view of its potential,
long-range, legal, ethical, social, medical, and economic imolications.

Significance : The traditional, oassive role that machines have played
in the delivery of health care is being radically altered by recent
developments in data processing, pattern recognition, and electronics
microcircuitry. Machines capable of emulating intelligent behavior
and making "judgments", independent of continuous physician supervision,
may soon be develooed for patient care; this study addresses the techno-
logical and social issues that such prospects raise.



48



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do WOT use this space)



U.S. DEPARTMENT OF
HEALTH, EDUCATION. AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RS 10043-02 BEI



PERIOD COVERED

October 1, 1978 to September 30, 1979



TITLE OF PROJECT (80 characters or less)

Fiber Optic Probes/Oxygen Probes



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



Chemist BEIB DRS

Mechanical Engineer BEIB DRS
Senior Investigator H IR MH



PI:


J.I.


Peterson


OTHER:


S.R.


Goldstein




R.M.


Wins low



COOPERATING UNITS (if any)

H-IR-MH



lab/branch
Biomedical Engineering and Instrumentation



SECTION

Chemical Engineering



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, Maryland 20205



TOTAL MANYEARS:

1.0



PROFESSIONAL:



1.0



CHECK APPROPRIATE BOX(ES)
D (a) HUMAN SUBJECTS

D (al) MINORS n (a2) INTERVIEWS



D (b) HUMAN TISSUES



D^c)



SUMMARY OF WORK (200 words or less - underline keywords)

Successful development of a fiber optic pH probe has provided a model
for the extension of this approach to the construction of other probes,
the most important being an oxygen probe . Effort during the previous
year had been devoted to attempting to develop a suitable color absorption
indicator for oxygen, a continuation of this effort led to the conclusion
that this was too difficult a problem to solve, so the work was redirected
toward evaluating the feasibility of using the principle of oxygen quenching
of fluorescence.



PHS-6040
(Rev. 10-76)



49



ZOl RS 10043-02 BEI

Objectives: Develop an oxygen sensor for tissue implantation to be
used in studies of oxygen transport during exercise.

Methods Employed: A fiber optic measurement of dye-indicator response
to oxygen.

Significance: In studies of abnormality in transport of oxygen to tissue
by blood during exercise, measurements of oxygen pressure in the tissue
can be used to determine the oxygen content of the blood supply via
the blood oxygen saturation curve (concentration vs. pressure).

Major Findings and Propo sed Course : The key ingredient for construction
of a fiber optic oxygen sensor is some color sensitive indicator for
oxygen. Efforts to develop a light absorption indicator (since none
IS available) were unsuccessful, and continued effort in this direction
would require more expenditure than seems justified. Use of the principle
of oxygen quenching of dye fluorescence was an alternative, and experiments
have shown that appropriate materials and dyes can be obtained which
are compatible with the use of plastic optical fibers. Work is continuing
on development of a probe using this principle.



50



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RS 10050-01 BEI



PERIOD COVERED

October 1, 1978 to September 30, 1979



TITLE OF PROJECT (80 characters or less)

Positron Emission Tomography Scanner



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI:
OTHER:



G. DiChiro
R.A. Brooks
V.J. Sank
W.S. Friauf
S.L. Leighton



Section Chief
Senior Staff Fellow
Research Physicist
Electrical Engineer
Mechanical Engineer



SN NINCDS
SN NINCDS
SN NINCDS
BEIB DRS
BEIB DRS



COOPERATING UNITS (if any)

SN NINCDS



lab/branch
Biomedical Engineering and Instrumentatio n



SECTION

EEES, MES



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, Maryland 20205



TOTAL MANYEARS:



3.0



PROFESSIONAL:



3.0



CHECK APPROPRIATE BOX(ES)
D'^a) HUMAN SUBJECTS

DX(al) MINORS Q (a2) INTERVIEWS



D (b) HUMAN TISSUES



D (c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

A custom PET scanner is being developed to provide compromises between
resolution, sensitivity, count rate capability, and cost that are optimal
for human neurological research requirements at NIH.



PHS-6040
(Rev. 10-76)



51



ZOl RS 10050-01 BEI

Objectives : Design and have built a PET scanner with higher resolution
than other custom or commercial machines, but without excessive compromise
of sensitivity or count rate capability.

Methods Employed : The design will feature a large number of BGO detectors
more tightly packed in a smaller ring than other designs, with electronic
advances to shorten the coincidence window to a minimum, thus easing
the random coincidence problem which is aggravated by a small ring.
A novel detector motion has been developed to further imorove resolution.

Major Findings : Analysis of the proposed design and experimental work
with BGO detectors both suggest that a considerable advance in PET scanning
is feasible.

Significance : PET imaging with a variety of positron emitting tracers
allows many metabolic processes to be studied soatially. The new scanner
will increase the spatial resolution which currently limits the potential
of the approach.

Publications :

Brooks, R.A., Sank, V.J., Talbert, A.J., and DiChiro, G. Sampling Requirements
and Detector Motion for Positron Emission Tomography. IEEE Transactions
on Nuclear Science, Vol. NS-26 (In Press).



52



StyllTHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RS 10051-01 BEI



PERIOD COVERED

October 1, 1978 to September 30, 1979



TITLE OF PROJECT (80 characters or less)

Monolithic Thermopile



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT



PI:


W.S. Friauf


OTHER:


C. Mudd




R. Berger



Electrical Engineer
Mechanical Engineer
Section Chief



EEES BEIB DRS
MES BEIB DRS
LTD NHLBI



COOPERATING UNITS (if any)

NBS



lab/branch
Biomedical Engineering and Instrumentation



SECTION

Electrical and Electronic Engineering Section



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, Maryland 20205



TOTAL MANYEARS:



PROFESSIONAL:



CHECK APPROPRIATE BOX(ES)
n (a) HUMAN SUBJECTS

D (al) MINORS n (a2) INTERVIEWS



D (b) HUMAN TISSUES



nfc) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

Process technology developed by the semiconductor industry should be
ideal for thermopile fabrication, allowing improvements which will be
reflected in advanced state of the art of micro-calorimetry , with many
applications to biochemical research. A monolithic thermopile has been
designed and will be fabricated in small quantities by NBS using conventional
integrated circuit technology. Analysis indicates that an order of
magnitude improvement in sensitivity relative to the present state of
the art should be possible with the same sample volume, with the potential
of maintaining this sensitivity for much smaller volumes.

Next steps include device fabrication and testing, adaptation of the
calorimeter to the new device, and system evaluation.



PHS-6040
(Rev. 10-76)



53



SMITHSONIAN SCIENCE INFORMATION EXCHANGE
PROJECT NUMBER (Do NOT use this space)



U.S. DEPARTMENT OF
HEALTH, EDUCATION, AND WELFARE
PUBLIC HEALTH SERVICE
NOTICE OF
INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RS 10052-01 BEI



PERIOD COVERED

October 1, 1978 to September 30, 1979



TITLE OF PROJECT



characters or less)



Laser Doppler Measurement of Tissue Blood Flow



NAMES, LABORATORY AND INSTITUTE AFFILIATIONS, AND TITLES OF PRINCIPAL INVESTIGATORS AND ALL OTHER
PROFESSIONAL PERSONNEL ENGAGED ON THE PROJECT

Physicist BEIB DRS

Electrical Engineer BEIB DRS

Biologist LTD NHLBI

Chief LTD NHLBI

Assistant Neurologist NB NINCDS

Research Physicist PSL DCRT



PI:


R.F. Bonner


OTHER:


T.Clem




P.D. Bowen




R.L. Bowman




A. Tahmoush




R. Nossal



COOPERATING UNITS (if any)

BEIB, DRS; LTD, NHLBI; NB, NINCDS; PSL, DCRT



lab/branch
Biomedical Engineering and Instrumentation



SECTION

Electrical Engineering



INSTITUTE AND LOCATION

DRS, NIH, Bethesda, Maryland 20205



TOTAL MANYEARS:



1.3



PROFESSIONAL:



0.8



0.5



CHECK APPROPRIATE BOX(ES)
n'fa) HUMAN SUBJECTS

Q (al) MINORS □ (a2) INTERVIEWS



n (b) HUMAN TISSUES



D (c) NEITHER



SUMMARY OF WORK (200 words or less - underline keywords)

A real-time tissue blood flow monitor has been developed based on the
velocity-dependent Doppler broadening of laser -light scattered by moving
red blood cells within living tissues. A physical theory has been developed
which explains the observed Doppler broadening of laser-light diffusing
through tissue and formed the basis of a new instrument design. This
instrument has demonstrated linear dependence on flow in a variety of
animal and human tissues . The instrument monitors pulsatile flow with
cardiac cycle as well as mean flow and has been used to characterize
transient changes in the microvasculature . A clinical investigation
of muscle blood flow at biopsy is being pursued in order to correlate
the state of the microvasculature with various muscular diseases . Further
development of the theory and instrumentation will be directed toward
extending the clinical and research use of the technique at a variety
of tissue sites.



PHS-6040
(Rev. 10-76)



54



ZOl RS 10052-01 BEI

Objective : The objective of this project is to develop and test a clinical
and research instrument, based on laser Doppler velocimetry, capable
of measuring changes in local tissue blood flow. The project has three
facets: (1) develop a physical theory of Doppler shifts from tissue,
(2) develop a simple-to-use instrument with flexible fiber optic light
path and electronic processor with linear response to a large range
of flow states, and (3) evaluate clinical usefulness of the device.

Major Results : A physical model has been developed which accurately
predicts the shape and half-width of the observed Doppler spectra from
various human tissues. This model clarifies the information content
in the detected signal and justifies a flow parameter based on the normalized
first moment of the power spectra. The instrument development has included
(1) that of a flexible fiber optic path capable of delivery and detection
of the laser-light to and from the tissue to be studied, and (2) an
electronic analogue processor to determine the normalized first moment
of the power spectrum corrected for noise sources. This electronic
processor gives a continuous output linearly-related to flow capable
of resolving the fine structure of the pulsatile flow with cardiac cycle
as well as slower changes in mean flow. Currently the ability of the
instrument to measure a broad range of blood flow levels in a number
of different tissues is being examined.

Proposed Course : A clinical protocol is being established to evaluate
its usefulness as a monitor of resting blood flow, reactive hyperemia,
and response of the microvasculature to external pressure, at a number
of muscle sites immediately prior to biopsy. This protocol proposes
to examine correlations between the state of the muscle microvasculature
and various muscle diseases. After this trial, it is proposed to extend
its clinical testing to the evaluation of skin graft viability and in
the evaluation of peripheral circulatory problems. Research use in
animals will also include evaluation of vasoactive pharmaceuticals.
Future refinement of the physical theory and electronic processor will
be directed toward extension of the device to tissues containing large
superficial vessels and with the aim of broadening the applicability
of the technique.



55



,;| I,. , M ,.. Ll,.UOl II. I wHMnllV'-
llwjLl.l I.UMI ch [00 NOT J. c till.



,).„, 1)1 I AH I Mr HI ul
IILHLril, . DUCAT lul., AMU WILIAKI
, UbLlC, 111 Airll -tllVlLL
NOTICE OF
INTRAMURAL RESEARCH PROJECT



I'll. ,in.| :.iJMi



ZOl RS 10053-01 BEI



I'bcTobeT'tl' 1978 to September 30, 1979

I'flTLt ur PHUJLCT (BO tli^rjcteri or lei;-)

Membrane Based Sampling Systems for in In Vivo and In Vitro Kinetic

Studies _

7a¥l~S, LAfaOHATOHY AND INSTITUTt AFF IL I AT I ONt,, AND TITLLS OF PRINCIPAL I NVLST IGATORS AND ALL OTHER
PROFESilONAL PtHSONNLL ENGAGt.O UN THE PKUJtCT

PI: P.M. Bungay Chemical Engineer BEIB DRS

OTHER: J. P. Froehlich Senior Investigator GRC NIA

R.L. Berger Section Chief LTD NHLBI

J. Fenstermacher Section Chief LCHPH DCT

R.L. Dedrick Section Chief ChES BEIB DRS



COOPtHATING UNITC (it any)

Gerontology Research Center-NIA; Laboratory of Technical Development-
NHLBI; Laboratory of Chemical Pharmacol ogy-DCT^

lab/branch

Biomedical Engineering and Instrumentation



Chemi cal Engineering

INSTITUTt AND LOCATION

_QR5^ !mU_B£tijeS(

'total MANYEARS:




land-2n?05



CHECK APPROPRIATE BOx(ES
Li (a) HUMAN SUBJECTS

[] (al) MINORA n (a2) IN TERVIEWS



PROFESSIONAL:



U (b) HUMAN TISSUES



lj;{c) NEITHER



SUMMARY OF WORK (200 words or lest - underline keywords)

Synthetic membranes are being utilized in kinetics studies to provide



a means for continuous sampling of the liquid from the system under

study. In one application sampling equipment is being developed for

in vitro study of calcium ion transport and calcium-ATPase activity

in suspension of sarcoplasmic reticulum vesicles prepared from homogenates

of rabbit muscle. In a second application a study of the mannalian

blood brain barrier permeability is being aided by the development of



an apparatus incorporating a sampler in an arteriovenous ex vivo shunt.
In the latter plasmapheresis application pooling the plasma filtrate
yields a single sample from which product of the plasma concentration
and time integral can be evaluated for a chemical administered to the
animal. Such sampling systems can be useful for the study of the kinetics
of other fluid phase systems for which a membrane can be found which
is permeable to one chemical of interest but impermeable to another
necessary reagent or sink. Thus, other applications might be found
in the areas of enzyme kinetics , pharmacokinetics , and the membrane
transDort of vesiclJe and cell susoeasjons^



56



ZOl RS 10053-01 BEI

Objectives : The principal objective is the development of the capability
for fluid sampling based upon synthetic membrane technology. In many
potential applications sampling by filtration or ultrafiltration may
be more appropriate than alternative sampling technique. Ultrafiltration
membranes allow the formation of samples representative of the free
concentration of small soluble substances. These membranes will retain
within the system under study macromolecules and those substances which
are bound to them as well as colloidal or cellular components of the
system. Other applications may call for the use of larger pore diameter
membranes of, for example, macromolecules are to be sampled as well.

Methods Employed : The sampling system generally consists of three elements:

(1) a module or modules containing sampling membranes, (2) sample collection

equipment, and (3) a means for controlling the rate of production of

sample. The membrane module is designed so that the membrane forms

a part of the wall of the channel through which the liquid to be sampled

flows. Only a small fraction of the liquid is diverted across the membrane

to form the sample. The sample is produced as a consequence of a difference

in pressure imposed across the membrane. The rate of production of

the sample is regulated either by controlling the transmembrane pressure

difference or through use of a sample metering pump.

Significance : Membrane sampling is being applied to studies of the
transport of calcium ions across sarcoplasmic reticulum (SR). The transport
studies are performed in vitro on a suspension of SR vesicles in buffer;
the vesicles being created by homogenizing rabbit muscle. The kinetics
of calcium uptake by or efflux from the vesicles can be followed by
monitoring the appearance or disappearance of calcium from the suspending
medium. Also, changes in levels of ATP and inorganic phosphate can
be used to infer the kinetics of the calcium dependent membrane ATPase.
The membrane in the sampler retains the vesicles (which are thought
to be in the range of 0.1-0.5 m in diameter), so that the sample is
representative of the suspending media.

A second application concerns in vivo studies of transport across the
blood brain barrier. The initial objective is the determination of


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Online LibraryNational Institutes of Health (U.S.). Division ofAnnual report : National Institutes of Health. Division of Research Grants (Volume 1979) → online text (page 18 of 24)