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

Report of program activities : National Institutes of Health. Division of Research Services (Volume 1975) online

. (page 4 of 11)
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Arteries During Steady and Pulsatile Flow. In Nerem, R.M. (Ed.): Fluid
Dynamic Aspects of Arterial Disease. Proceedings From a Specialists Meeting
on Fluid Dynam ic Aspects of Arterial Disease , Columbus, Ohio, September 19-20,
1974, pp. 5-S.



31



Project No. ZOl RS 00006-03 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Chemical Engineering Section
3- Bethesda

PHS-NIH

Individual Project Report

July 1, 1974 through June 30, 1975

Project Title: Multicomponent Plastics in Biomedical Use

Previous Serial Number: DRS-BEIB-5

Principal Investigator: Henry L. Gabelnick

Other Investigator: Margaret L. Wehling

Cooperating Units: None

Man Years :

Total: 0.6
Professional: 0.3
Other: 0.3

Project Description:

Objectives : Extend definition of the interaction of plastic systems with the
biological environment, emphasizing the kinetics of additive elution from
polymers and absorption of body constituents.

Methods Employed : Determination of elution rate of migrating species via
quantitative analytical techniques. Parameters under investigation include
fluid composition and flow conditions.

Major Findings ; Refined analjrtical techniques enable evaluation of the
di-2-ethylhexylphthalate-polyvinyl chloride system exposed to a soybean
emulsion "pseudo- serum."

Desorption of phthalate from surgical grade polyvinyl tubing (3/16" I.D.) was
independent of flow rate over the range 100 to 300 ml/min. However, the rate
of uptake of phthalate by the pseudo-serum increased by a factor of two when
the lipid concentration was increased from 100 to 300 mg^.

Proposed Course : Project terminated in December 1974 due to departure of the
principal investigator.

Keyword Descriptors : Phthalates, plasticizes elution, vinyl tubing, desorp-
tion kinetics

Honors and Awards : None

Publications : None 32



Project No. ZOI RS 00005-03 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Chemical Engineering Section

3 . Bethesda

PHS-NIH

Individual Project Report

July 1, 1974 through June 30, 1975

Project Title: Thermomicrography

Previous Serial Number: None

Principal Investigators: John I. Peterson

Other Investigators: Robert L. Bowman

Cooperating Units: LTD-NHLI

Man Years:

Total: 1.3
Professional: 0.8
Other: 0.5

Project Description:

Objectives : Develop a method for microscopic observation of biological cells
by their thermal effects.

Methods Employed : Investigation of the possible use of the optical-thermal
properties of the cholesteric mesophase ("liquid crystals").

Major Findings ; The well-known and previously investigated properties of
cholesteric esters have been based on materials of undocumented and probably
low purity. The accepted theoretical model for their behavior is imtenable
from the chemical point of view. The investigation of highly purified
material shows behavior which is different and possibly more useful than
previously observed, as well as being divergent from that expected.

Significance : A technic of microthermography would be useful for cell
calorimetry and other energy studies on an individual cell basis, and could
provide a possible route to facilitation of screening studies involving
various kinds of cellular reactions.

Proposed Course : Verification of conclusions derived to date and extension
through continued investigation.

Keyword Descriptors ; Thermography, liquid crystals, purification, cholesteric
esters.

Honors and Awards ; None

Publications : None ^^



Project No. ZOl RS 00007-01 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Electrical and Electronic
Engineering Section

3. Bethesda

PHS-NIH

Individual Project Report

July 1, 197^ through June 30, 1975

Project Title: Investigation of Oxidative Metabolism and Potassium Kinetics
in the Cat Brain

Previous Serial Number: DRS-BEIB-7

Principal Investigators: William H. Schuette, DarrellV. Lewis

Cooperating Units: EEG-NINDS

Man Years :

Total: 2,0
Professional: 1.5
Others: 0.5

Project Description:

Objectives : ( 1 ) Develop and apply new and improved techniques for analyzing
oxidative metabolism of the cat brain and correlating these results to simul-
taneous extracellular potassium kinetic measurements.

(2) Determine the Qio of potassium kinetics in the cat hippocampus.

(3) Validate oxidative metabolism measurements obtained by NADH fluorescence
techniques with direct measurement of cortical oxygen consumption.

Methods Employed : NADH fluorescence measurements are made with a unique
two-channel fluorometer.

Q-| Q measurements are made by cooling the brain with an "Elliott ' s B" solution
drip while measuring local temperature with a thermistor. Potassium kinetics
are measured with a potassium sensitive microelectrode following electrical
stimulation.

Cortical oxygen consumption is determined from the combination of oximetry and
flow of blood drained from the sagittal sinus of cats.

Major Findings ; (l) Clearance of potassium following stimulation of the
brain is an exponential process.



34



(2) The Qjo foi" this clearance is approximately 2.1.

(3) A linear relationship exists between the amount of potassium released
following a stimulus to the train and the time integral of the NADH fluores-
cence signal.

(4) NADH fluorescence signals appear to be related to direct oxygen
consumption measurements.

Significance : Evidence for potassium clearance being an active process has
been reinforced.

The utility of NADH fluorescence as an indicator of oxidative metabolism has
been demonstrated.

Proposed Course : Refinement and extension of work done to date.

Keyword Descriptors : NADH, fluorescence, potassium, kinetics, oximetry

Honors and Awards : None

Publications :

1. Lewis, D.V., O'Connor, M.J. and Schuette, W.H.: Oxidative Metabolism
During Recurrent Seizures in the Penicillin-Treated Hippocampus.
Electroencephalogr . Clin Neurophysiol . 36: 347-356, 1974.

2. Schuette, W.H., Whitehouse, W.C., Lewis, D.V., O'Connor, M.J. and

Van Buren, J.M. : A Television Fluorometer for Monitoring Oxidative Metabolism
in Intact Tissue. Med . Instrum . 8: 331-333, 1974.

3. Lewis, D.V. and Schuette, W.H. : NADH Fluorescence and (K J Changes During
Hippocampal Electrical Stimulation. J. Neurophysiol. 38: 405-417, 1975.



35



Project No. ZOl RS 00008-03 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Electrical and Electronic
Engineering Section

3- Bethesda

PHS-NIH

Individual Project Report

July 1, 1974 through June 30, 1975

Project Title: Diagnostic Ultrasound

Previous Serial Number: DRS-BEIB-8

Principal Investigators: James M. Griffith, Walter L. Henry, William R. Brody,

Steven Charles

Other Investigators: David lutyerowitz, Barry J. Maron, Stephen E. Epstein

Cooperating Units: CB-IR-NHLI, SU-IR-NHLI, IR-NEI

Man Years:

Total: 3.5
Professional: 2.0
Others: 1.5

Project Description:

Objectives : (l) Noninvasively obtain dynamic images and measurements of
cardiac structure and function and assess for diagnostic and therapeutic
piirposes.

(2) Noninvasively obtain Images and measurements of ophthalmic structure and
assess for diagnostic and therapeutic purposes.

(3) Noninvasively obtain dynamic measurements of blood flow in circulatory
vessels.

Methods Employed ; A previously reported real-time, two-dimensional sector
scanner was refined and used effectively in several new research applications.

The sector scanner technique was extended to ophthalmological applications.

Principles of high resolution radar and communication theory are being applied
to doppler flowmeter design for improved resolution.

A moving- trace monitor system was developed which allows two seconds of EKG
to be recorded on each frame of real-time two-dimensional echogram.



36



d



i



Major Findings ;

(1) Mitral valve orifice area can be accurately measured by real-time
two-dimensional echocardiography.

(2) Two-dimensional echocardiography is a significant new tool for the
differential diagnosis of anomalies of the great arteries.

( 3 ) Mechanical sector scanning in real time is applicable to ophthalmic
scanning; this considerably reduces examination time.

Significance : Safe noninvasive methods for making quantitative and qualitative
physiologic measurements are of substantial value for research and diagnostic
purposes.

Proposed Coiirse : The doppler flowmeter design will be improved so that
useful velocity and range resolution are obtained. Then it may be possible
to combine a flowmeter and a sector scanner so that real-time two-dimensional
imaging is available simultaneously with flow measurement.

Keyword Descriptors : Ultrasoimd, Pulse Echo, doppler

Honors and Awards : None

Publications :

1. Griffith, J.M. and Henry, W.L. A Sector Scanner for Real Time Two-
Dimensional Echocardiography. Circulation , XLIX: 114-7-1152, 1974.

2. Wtyerowitz, P.D., Griffith, J.M., Roberts, A.J., Harrison, L.H., Henry,
W.L., and Mcintosh, G.L. Long-Term Canine Model for Echocardiography.
Am. J. Cardiol. 34: 72-74, 1974.

3. Griffith, J.M. and Henry, W.L. Switched Gain: Simplifies Ultrasonic
Measurement of Cardiac Wall Thickness. In Proceedings of the 27th Annual
on Engineering in Medicine and Biology 1974, Philadelphia, Pennsylvania,
Arlington, Va., The Alliance for Engineering in Medicine and Biology, 1974,
Vol. 16, p. 264.

4. Wfcrerowitz, P.D., Brown, J.W., Harrison, L.H., Griffith, J.M., Henry, W.L.
and Mcintosh, C.L. A Comparison of Simultaneous Echocardiographic and
Electromagnetic Flowmeter Determination of Stroke Volume, Supplement III to
Circulation , Vols. 49 and 50, October 1974.

5. Henry, W.L., Griffith, J.M. , Michaelis, L.L., Mcintosh, C.L., Morrow, A.G.,
and Epstein, S.E. Quantitation of the Mitral Orifice Area by Real-Time
Two-Dimensional Echocardiography. Supplement III to Circulation , Vols. 49

and 50, October 1974.

6. , Epstein, S.E., Griffith, J.M., Goldstein, R.E., Redwood, D.R.

Effect of Prolonged Space Flight on Cardiac Function and Dimensions. Am. J.
Cardiol. 35: 143, 1975.



37



7. Griffith, J.M. and Henry, W.L. A Moving-Trace Monitor for Video
Systems. Med . Instrum . 9: 73, 1975.

8. Henry, W.L., Maron, B.J., Griffith, J.M. , Redwood, D.R., and Epstein, S.E.
Differential Diagnosis of Anomalies of the Great Arteries by Real-Time
Two-Dimensional Echocardiography. Girciolation 51: 283-291, 1975.

9. , Clark, C.E., Griffith, J.M. , and Epstein, S.E. Mechanism of
Left Ventricular Outflow Obstruction in Patients with Obstructive Asymmetric
Septal Hypertrophy (Idiopathic Hypertrophic Subaortic Stenosis). Am. J.
Cardiol. 35: 337-345, 1975.



I



38



Project No. ZOl RS 00009-05 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Electrical and Electronic
Engineering Section

3 . Bethesda

PHS-NIH

Individual Project Report

July 1, 1974 through June 30, 1975

Project Title: Nuclear Magnetic Resonance Techniques for Biochemical Analysis

Previous Serial Number: DftS-BEIB-6

Principal Investigators: Thomas R. Clem, Walter S. Friauf, Edwin D. Becker

Other Investigator: James A. Ferretti

Cooperating Units: LCP-NIAMDD, PSL-DCRT

Man Years:

Total: 2.0
Professional: 1.5
Other: .5

Project Description:

Objectives : Innovate and implement improved methods for structural elucida-
tion of organic molecules by means of muclear magnetic resonance with empha-
sis on flexibility and convenience in selecting specific nuclei for study and
the particular type of test performed.

Methods Employed : Develop and evaluate techniques for improving sensitivity
and versatility, including use of a superconducting magnet, piilse train exci-
tation with digital programming of the sequences, heteronuclear decoupling,
real-time computerized data acquisition, digital averaging, phase correction,
matched filtering, Fourier Transformation, and printout of spectra. Develop
and evaluate Rapid Scan Fourier Transform NMR techniques as an intermediate
alternative to CW and pulsed FT methods. Develop and evaluate improved
methods of RF generation for greater reliability and flexibility.

Major Findings : NMR techniques can be used to routinely obtain parameters of
organic molecules beyond those previously available including nuclei other
than 1h and ^^C.

Significance : Technique offers unprecedented capability for elucidation of
organic molecule structure and, in particular, the location of -^C, et al,
atoms. The high field strength of the superconducting magnet enables finer
resolution than is obtainable with most other -^^C NMR apparatus.



39



Proposed Coiirse ; Modifications with a second superconducting magnet to
enable experiments with full-time application to 13c and related atoms.

Keyword Descriptors: Nuclear Magnetic Resonance, Fourier Transform NMR.



Honors and Awards : None

Publications :

Cohen, J.S., Bradley, R.B., Clem, T.R.: pH Dependence of the 13c Spin-Lattice
Relaxation Rate of the Carboxyl Carbon of Acetic Acid. J. .Am. Chem Soc . 97:
908-909, 1975.

Wasylishen, R.W., Clem, T.R., Becker, E.D. Nuclear Magnetic Resonance
Chemical Shifts of Some Monosubstituted Isothiazoles. Can . J . Chem . 53:
596-603, 1975.



40



Project No. ZOl BS 00010-04 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Electrical and Electronic
Engineering Section

3 . Bethesda

PHS-NIH

Individual Project Report

July 1, 1974 through June 30, 1975

Project Title: Measurement of Low Level, Rapid Chemical Reaction Rates by-
Laser Jump, Temperature Jump, and Stopped Flow Techniques

Previous Serial Numher: DRS-BEIB-9

Principal Investigators: Michael Greifner, P. Boon Chock

Other Investigators: None

Cooperating Units: LC-IR-NHLI

Man Years:



Total:


1.0


Professional:


.75


Other :


.25



Project Description:

Objectives : Measure incremental parameter changes corresponding to Important
biochemical reactions over a wide dynamic range. Develop a system capable of
detecting and displaying chemical reaction rise times of less than 100
nanoseconds.

Methods Employed : Light absorption and fluorescence are monitored with
photomultipliers. Dynode switching provides wide dynamic range without
impairment of frequency response, linearity or accuracy. High intensity
pulsed light sources improve the singal to noise ratio of nanosecond absorp-
tion measurements. Signal averaging techniques recover low level signals
otherwise obliterated by noise. Improved data processing reduces investigator
evaluation time for a typical experiment from weeks to days.

Major Findings : Development of new stopped flow cell reduces dead time from
milliseconds to microseconds. Allows researchers to record reaction rates
previously masked in mixing time of two chemicals. Stopped flowmeter with
increased sensitivity provides an order of magnitude improvement in absorption
level detection over commercially available instruments. High sensitivity is
required to detect especially low level enzyme reactions.



41



Significance: Improved system sensitivity and frequency response enable new
exploratory investigations into the complex mechanisms of various enzyme
functions. State-of-the-art instrumentation for temperature jump apparatus
and stopped flowmeters can provide information on the incremental, fast
interactions between antibiotics with enzymes or proteins.

Proposed Course : Complete evaluation of stopped flowmeter reaction times.
Patent new stopped flow cell. Design and develop multi-mix stopped flow
apparatus. Design and develop pulse unit for high intensity lamps. Test
and evaluate temperature jump apparatus. Design and develop instrumentation
for detection of fluorescence and absorption time constants of laser
temperature jump.

Keyword Descriptors : Laser temperature jump, stopped flow.

Honors and Awards : None

Publications : Rhee, S.G., Greifner, M.I., and Chock, P.B. ATP Determination
by Stopped-Flow Method. Journal of Analytical Biochemistry (in press).



4



A



i,2



Project No. ZOl RS 00011-02 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Electrical and Electronic
Engineering Section

3. Bethesda

PHS-NIH

Individual Project Report

July 1, 1974 through June 30, 1975

Project Title: Electrical Safety Program for Clinical Center Patients and
Patient Care Areas.

Previous Serial Number: None

Principal Investigator: Roland Corsey

Other Investigators: Corwin Strong, Anthony Vita, Walter S. Friauf

Cooperating Units: ADM-CC, SMS-BEIB

Man Years:

Total: 1.0
Professional: 1.0
Other:

Project Description:

Objectives : Establish a patient environment free of shock hazards and assure
Clinical Center compliance with accreditation requirements regarding electri-
cal safety.

Methods Employed ; Establish NIH standards for the evaluation of commercial
and non- commercial medical equipment; establish a testing program for all
patient-contact electrical equipment; train nursing staff on the fundamentals
of electricity and electrical safety; investigate and report on electrical
accidents; conduct sur-veys of patient care areas to correct electrical
hazards in grounding and power distribution; advise medical and nursing
staff on new equipment purchases; participate in shaping of national,
electrical safety standards.

Major Findings : The test program for medical equipment has uncovered
instances of high electrical leakage current and poor grounding. Surveys of
patient care areas have established the need for improved grounding and
power distribution systems in critical care areas.

Significance : In critical care areas such as catheter laboratories, operating
rooms and intensive care areas, the likelihood of accidental electricution
has been reduced.



43



Proposed Course :

1. Train additional personnel on the fundamentals of electrical safety.

2. Extend the patient care area surveys to non-critical areas.

3. Extend the equipment testing program to test all new equipment before it
is put into service.

Keyword Descriptors ; Medical equipment, electrical safety standards,
critical care areas.

Honors and Awards : None

Publications :

Friauf, W.S.: Test Equipment for Hospital Safety Programs. In Proceedings
of the 27th Annual Conference on Engineering in Medicine and Biology, 197.4 ,
Philadelphia, Pennsylvania . Arlington, Va., The Alliance for Engineering in
Medicine and Biology, 1974, Vol. 16, p. 496.



f



4^



Project No. ZOl RS 00012-0-4 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Mechanical Engineering Section

3. Bethesda

PHS-NIH

Individual Project Report

July 1, 1974 through June 30, 1975

Project Title: Atraumatic Electrical Sensing in the Human Brain Cortex

Previous Serial Number: DRS-BEIB-12

Principal Investigators: Seth Goldstein

Other Investigators: Edward M. Schmidt, John Van Buren, John Oakley

Cooperating Units: LNLC-NINCDS, SN-NINCDS

Man Years:

Total: 1.5
Professional: 1.0
Others : . 5

Project Description:

Objectives : (l) Achieve stable electrode location with respect to an active
neuron for reliable actue extracellular recording of human brain cell
acitivity within the pulsating cortex at prescribed depths up to 0.5 cm with
minimum tissue damage.

(2) Extend this technique to achieve intracellular recording from the
pulsating cortex.

Methods Employed : A microelectrode is supported by a gas bearing assembly and
held within the cortex at the desired insertion angle. A fine lead screw is
actuated by gas thrust bearings to retain the "floating" action during
electrode depth adjustment. An electrocortigram is simultaneously obtained
from the adjacent area of cortex.

Major Findings : The device has been successfully used to obtain high quality
extracellular himian recordings for prolonged durations. Intracellular
recordings using glass micropipette electrodes have been obtained from
pulsating monkey brain cortex.

Significance : Single-cell electrical recording from cerebral cortex in humans
has been limited because of difficulty in atraumatically eliminating the
effects of cortical motion. This new method is expected to markedly improve
the acquisition of valid information necessary to enhance understanding of
brain function and epilepsy.



45



Proposed Course: Extension of the technique to intracellular studies in
human brain cortex; refinement of technique and apparatus, if necessary;
clinical applications; extension of device family for related types of
measurement requirements.

Keyword Descriptors : Single-cell electrical recording, extracellular
electrical recording, intracellular electrical recording, neuroelectric
recordings.

Honors and Awards : Goldstein, S.R. : Electrode Insertion Device for
Neuroelectric Recordings. U.S. Patent No. 3,8^41,310 (October 15, 1974).

Publications :

Goldstein, S.R., Schmidt, E.M. , Bierley, F.L., and Bak, M. : A Gas Bearing
Mechanism for Atraumatic Electrical Recording from Individual Neurons in
Human Cerebral Cortex. Transactions of the American Society of Mechanial
Engineers, Journal of Dynamic Systems, Measurements and Control (in press).



LвВђ



46



Project No. ZOl RS 00013-01 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Mechanical Engineering Section

3. Bethesda

PHS-NIH

Individual Project Report

July 1, 197A through June 30, 1975

Project Title: In Vitro Muscle Studies/Hypertrophy

Previous Serial Number: None

Principal Investigators: Edward Lebowltz, Lawrence Thibault

Other Investigators : None

Cooperating Units: CB-NHLI

Man Years:

Total: 1.0
Professional: 1.0
Other :

Project Description:

Objectives : (l) To explicate the mechanism of cardiac hjrpertrophy in vitro
using cat papillary muscle preparations.

( 2 ) To investigate phosphorylation of papillary muscle in vitro ( organ
culture ).

Methods Employed : Experimental apparatus has been developed in which cat
papillary muscle is suspended in a constant temperature recirculating medium.
PO2 and PCO2 of the medium are monitored as electrical stimuli are applied
to the preparation.

Forces of contraction are measured concomitantly with gas tensions. Tissue
growth is detected optically.

Major Findings : The preparations can be maintained viable for several days.
This enables both phosphorylation and hypertrophy for adequate periods to
reliably analyze both of these phenomena in vitro .

Significance : More detailed knowledge of hypertrophic mechanisms in cardiac
muscle bears directly upon clinical diagnosis and therapy. Quantification of
phosphorylation in cardiac muscle should contribute to the fundamental under-
standing of cardiac contractility.

Proposed Course : Improve and extend experimentation and analysis.

47



Keyword Descriptors : Hypertrophy, phosphorylation, organ cultiire, ^

papillary muscle. %

Honors and Awards : None

Publications : None



4



48



Project No. ZOl RS 00014-01 BEI

1. Biomedical Engineering and
Instrumentation Branch

2. Mechanical Engineering Section

3. Bethesda

PHS-NIH

Individual Project Report

July 1, 1974 through June 30, 1975

Project Title: Neural Trauma
Previous Serial Number: None

Principal Investigators: Lawrence Thiabult, Thomas Gennarelli
Other Investigators: None
Cooperating Units: Georgetown University-
Man Years:

Total : 1.0
Professional: 1.0
Other : .

Project Description:

Objectives : To determine the effects of mechanical strain on nerve tissue
function. To investigate the role of mechanical strain on nerve tissue mem-
brane transport regulations.

Methods Employed : Equipment has been developed which permits controlled loads
to be applied to isolated neural tissue. Mechanical stress and strain are
measiired concomitantly with electrophysiological parameters and associated
biochemical changes.

Major Findings : Mechanical strain affects neural function. Compound action
potentials are modulated by strain, both fully reversibly and irreversibly
depending upon the level of strain. Biochemical changes, e.g. potassium
movement, occur simiiltaneously, suggesting membrane permeability changes.

Significance : Elucidation of the effects of membrane strain on chemical
transport processes contributes substantially to the basic understanding of
fundamental physiological mechanisms.

Proposed Course : Refine and extend experimental and analytical techniques for
nerve cells and other tissues.

Keyword Descriptors : Nerve tissue, neural trauma, membrane transport,
mechanical strains.



49



Honors and Awards: None



Publications :



Gennarelli, T.A. and Thibault, L,E.: Functional response of the central
nervous system to controlled inertial loading. In Proceedings of the 27th


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Online LibraryNational Institutes of Health(U.S.). Division of RReport of program activities : National Institutes of Health. Division of Research Services (Volume 1975) → online text (page 4 of 11)