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National Institutes of Health (U.S.). Biomedical E.

Annual report: National Institutes of Health. Division of Research Services. Biomedical Engineering and Instrumentation Branch (Volume 1984) online

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original preamplifier. A command from the computer terminal selects the
scanning mode and connects the proper preamplifier into the system.



Page 88

ZOl RS 10155-02 BEI
0B3ECTIVES: To produce a detector system for a fluorescence microscope capable
of providing both a noomal output suitable for a display monitor and a
spatial-wavelength output suitable for determing fluorescent intensity changes
as a function of position and time.

METHODS EMPLOYED: A model 125^ B silicon intensified target vidicon detector
and a model 1216 controller, both manufactured by Princeton Applied Research,
have been interfaced to a Digital Equipment Corporation DECLAB-1 1/MNC
miniconputer. A FORTRAN program has been developed to permit control of the
scanning parameters of the vidicon and collect the output data. The program
is interactive and allows for changed of parameters with error checking to
reduce the possibility of damage to the detector by overscanning a small
target area.

The vidicon has been mounted on the fluorescence microscope to permit either
normal observation of the image plane or observation of a slit after passing
through a monochromator.

A modification has been made to the vidicon controller and an electronic
circuit constructed to produce a cortposite video signal suitable for display
monitors or for storage on video tape recorders. Due to the charge coupled
integrating preamplifier used in the 125^ detector, an image of low horizontal
resolution (about 100 television lines) was obtained. To improve the picture
resolution, a fast low noise FET preamplifier was constructed and mounted
inside the preamplifier compartment directly above the existing preamplifier.
A coRfiputer controlled relay, mounted between the two preamplifiers, switches
the vidicon output from the original non-standard scan system to the standard
video (including the fast preamplifier) scan. To increase the dynamic range
of the imaging system, a video processing amplifier was constructed and
included in the system. The processing amplifier permits the researcher to
adjust the video output signal to a standard video level from the wide range
of brightness levels that he may encounter.

SIGNIFICANCE: The ability to switch from a normal composite video signal to a
programmed non-standard video scan provides an extra level of sophistication
for microscope work. The actual object seen by the vidicon can be observed
and aligned to an optimum configuration before switching to the wavelength
analysis mode. This is expected to be highly attactive to workers in this
field.

PROPOSED COURSE: To establish a satisfactory high resolution image on the
monitor display. To analyze the wavelength-position data for accuracy. To
provide for time resolved information within the limits of the detector
readout time.



DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT



Page 89



PROJECT NUMBER

ZOl RS 10156-02 BEI



PERIOD COVERED

October 1, 1983 to Septembe r 30, 1984

TITLE OF PROJECT ^80 characters or less Title must lit on one line befween the borders )

Differential Scanning Calorimeter



PRINCIPAL INVESTIGATOR (List other professional personnel betow the Principal Investigator j (Name, title, laboratory, and institute aHiliation)

C.P. Mudd, Biomedical Engineer, ACES, BEIB, DRS
T. Talbot, Mechanical Engineer, ACES. BEIB, DRS
R.L. Berger, Physicist, LTD, NHLBI
P.D. Ross, Physical Chemist A LMB, NIADDKD



COOPERATING UNITS (it any)

LTD, NHLBI

A LMB, NIADDKD



LAB/BRANCH

Biomedical Engineering and Instrumentation



SECTION

Applied Clinical Engineering Section



INSTITUTE AND LOCATION

DRS. National Institutes of Health, MD 20205



TOTAL MAN-YEARS:



0.1



PROFESSIONAL



0.1



OTHER:



CHECK APPROPRIATE BOX(ES)

D (a) Human subjects
D (a1) Minors
D (a2) Interviews



D (b) Human tissues M (c) Neither



SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided.)

The transfer of sensor design and modelling techniques to the field of
differential scanning calorimetry from earlier work in differential heat
conduction calorimeter has resulted in two models of differential scanning
calorimeters which should satisfy the sensitivity and scan rate requirements.
One system uses two sensors and takes the difference electronically while the
other system used only one sensor which operates as a null detector in two
match thermal channels.



Page 90

ZOl RS 10156-02 BEI
OBJECTIVES: To scan or change the temperature of a sample and observe small
changes in the heat content of the sample which are attributed to physical
changes within the sample (e.g. conformation changes in proteins) and not the
scanning rate.

SIGNIFICANCE: The increasing use of DSC (differential scanning calorimetry)
in biological work is an indication of its usefulness in determining the
energy levels involved in the conformation changes in large biological
molecules. The sensitivity of current instruments limits their use to
applications involving relatively large amounts of heat. If the sensor design
developed for the differential batch calorimeter can be successfully
implemented into a DSC, the sensitivity should increase by a least a factor of
10.

PROPOSED COURSE: Both of the proposed models offer the promise of increasing
the sensitivity. Each model has its own advantages and disadvantages. The
single sensor design does not require careful matching of amplifier gains and
sensor sensitivities but does require a more carefully matched thermal pathway
for the heat flow resulting from the scanning. The two sensor design uses a
simple thermal pathway which is easily balanced but requires careful matching
of the sensors and amplifier gains.

The next phase will involve implementing these two designs into hardware and
evaluating them.



DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT



Page 91

PROJECT NUMBER

ZOl RS 10157-02 BEI



PERIOD COVERED

October 1, 1983 to September 30, 1984



TITLE OF PROJECT (SO characters or less Title must fit on one line between the tmrders )

Temperature Controlled Chamber for X-ray Diffraction Specimens



PRINCIPAL INVESTIGATOR (List other prolessional personnel tw/ow the Principal Investigator ) (Name, title, laboratory, and institute aHiliation)

C.P. Mudd Biomedical Engineer, ACES, BEIB,DRS

H.W. Tipton Mechanical Engineering Tech. ACES, BEIB, DRS

A.V. Parsigian, Research CR,PSL

B.K. Lee, Researcher CR,PSL



COOPERATING UNITS (il any)

DCRT, CR-PSL



LAB/BRANCH

Biomedical Engineering and Instrumentation



SECTION

Applied Clinical Engineering Section



INSTITUTE AND LOCATION

DRS. National Institutes of Health, MP



20205



TOTAL MAN-YEARS:



0.1



PROFESSIONAL:



0.1



OTHER:



CHECK APPROPRIATE BOX(ES)

D (a) Human subjects
D (a1) Minors
D (a2) Interviews



n (b) Human tissues ^ (c) Neither



SUMMARY OF WORK (Use standard unreduced type. Do not exceed the space provided.)

A proto-type chamber was constructed of lexan with a 1 cm diameter
wi ndow to allow th e x-ray beam to enter the chamber . The specimen
in 3 holder next to the beryllium window. The edge of the holder
to the lexan case to preserve the vacuum seal while the center ar
holder is mounted to a Peltier solid state heat pump . The other s
heat pump is connected to a heat sink. A thermistor mounted n
specimen in the holder controls the heat pump to keep the specimen
temperature . The film plate is mounted inside the chamber on an
bracket. The chamb.er will hold a vacuum of 0.01 atm while the
keeps the specimen at any temperature between 4°C and 70°C with a st
+ 0.2°C.



beryl lium
is mounted
is mounted
ea of the
ide of the
ext to the
at the set



adjustable
control ler
abi 1 1 ty of



Page 92
ZOl RS 10157-02 BEI



OBJECTIVES: There are two primary objectives:



(1) To reduce the temperature-motion-artifacts of the sample which tend to
blur the x-ray image.

(2) To reduce the scattering of the x-rays caused by the air molecules between
the sample and the film plate.

SIGNIFICANCE: The control of the sample temperature and reduction in the air
scattering should yield a dramatic increase in the reproducibility and
sharpness of the diffraction images. In this design there is only one
beryllium window between the sample and the film plate.

PROPOSED COURSE: The prototype is now in operation in the investigators lab
and is undergoing evolution. No additional development anticipated.



DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT



Page 93

PROJECT NUMBER

ZOl RS 10158-02 BEI



PERIOD COVERED

October 1, 1983 to September 30, 198^+



TITLE OF PROJECT (80 characters or less. Title must tit on or^e line between fhe borders.)

Isolated Heart Perfusion



PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator.) (Name, title, laboratory, and institute affiliation)

M.A. MacCollum, Mechanical Engineer, ACES, BEIB, DRS,
Greg Ribakove, M.D. Heart Surgery, NHLBI



COOPERATING UNITS (if any)

Surgery Branch, NHLBI



LAB/BRANCH

Biomedical Engineering and Instrunentation



SECTION



Applied Clinical Engineering Section



INSTITUTE AND LOCATION

DRS, National Institutes of Health, MD 20205



TOTAL MAN-YEARS:



1.2



PROFESSIONAL:



A



OTHER:



1.1



CHECK APPROPRIATE BOX(ES)

n (a) Human subjects
n (a1) Minors
D (a2) Interviews



n (b) Human tissues ^ (c) Neither



SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided )

An apparatus for perfusion of isolated rat hearts has been developed which
circulates a buffered blood analog. This device is used to investigate
biochemical and physiological parameters of the heart, including blood
pressure, pulse pressure, cardiac output, tissue pH and others. The system
allows investigators to induce temporary cardioplegia, during which
pharamacologic agents may be introduced into the modes of operation:
working heart, ischemia (both warm and cold) and Langendorf aortic
perfusion. Comparing the pre- and post-plegic parameters allow the
investigators to assess the ability of certain drugs and procedures to
sustain cellular life through ischemic periods.

The results gained from the isolated heart experiments will be tested in
large animals in vivo, using the same parameters along with animal survival
after surgery.

Engineering refinements in the perfusion circuit described above are
completed and the system is fully operational.



Page 94



DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZQl RS 10159-03 BEI



PERIOD COVERED

October 1, 1983 to September 30, 198^^



TITLE OF PROJECT (80 characters or less Title must tit on one line befween the borders.)

Pathophysiology of Cachexia in Sarcoma Patients



PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator ) (Name, title, laboratory, and institute attiliation)

R.Corsey Electronic Engineer BEIB, DRS

Others:

3, A. Norton Section Chief SURG, NCI

a.F. Moley Research Associate SURG, NCI



COOPERATING UNITS (il any)

Anesthesiology Service, Clinical Center, NIH (D.E. Lees)
Nutrition Department, Clinical Center, NIH



LAB/BRANCH

Biomedical Engineering and Instrumentation



SECTION

Applied Clinical Engineering Section



INSTITUTE AND LOCATION

DRS, National Institutes of Health, MP 20205



TOTAL MAN-YEARS:

2.0



PROFESSIONAL;



1.5



OTHER:



0.5



CHECK APPROPRIATE BOX(ES)

^ (a) Human subjects
D (a1) Minors
n (a2) Interviews



D (b) Human tissues D (c) Neither



SUMMARY OF WORK (Use standard unreduced type. Do not exceed the space provided.)

The first phase of this study has demonstrated that patients with metastatic
disease have higher levels of energy expenditure than controls, and patients
with extremity sarcomas have slightly higher levels of energy expenditure than
controls. The next phase will determine if glucose oxidation, whole body
protein turnover and potassiun ^0 levels are different in preoperative sarcoma
patients from controls. Sarcomas are useful for understanding the
pathophysiology of cachexia in that they usually do not alter the patient's
ability to aliment himself, they are metabolically active and patients bearing
than have been shown to have an increase in glucose consumption across tumor -
bearing limbs. Stable isotopes in the forms of 13C-glucose and 15N-giycine
and 13C-leucine are not radioactive and are very safe to administer. The
study will determine if any difference demonstrated by measurements of
isotopes can be correlated with timor size or growth.



DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT



Page 95



PROJECT NUMBER

ZOl RS 10i62-0i^ BEI



PERIOD COVERED

October 1, 1983 to September 30, 1984



TITLE OF PROJECT (80 characters or less. Title must tit on one line between the borders.)

Wound Healing: Biology and Rheology



PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator ) (Name, title, laboratory, and institute affiliation)

Thomas L. Talbot, MS, ACES, BEIB

Walter T. Lawrence M.D., C. Surgery, NCI

Lawrence £. Thibault, ScD. Bioengineering Dept, Univ. of Pa



COOPERATING UNITS (if any)

DRS, NCI, University of Pa, Philadelphia, Pa



LAB/BRANCH

Biomedical Engineering and Instrumentation



SECTION

Applied Clinical Engineering Section



INSTITUTE AND LOCATION

DRS, National Institutes of Health, MD 20205



TOTAL MAN-YEARS



1.2



PROFESSIONAL:



1



OTHER



0.2



CHECK APPROPRIATE BOX(ES)

D (a) Human subjects
n (a1) Minors
n (a2) Interviews



n (b) Human tissues



K (c) Neither



SUMMARY OF WORK (Use standard unreduced type Do not exceed the space provided.)

Preliminary studies have been completed with swine models . These studies
involved stamping an i nde l ible gird (lOcmxlOcm) on the ski n of the swine, and
the excision of a 1 cm by 10 cm strip of the skin out of the grid area, and
finally approximating the incision edges with silk sutures. Photographs of
the grid were taken before excision, after excision, and after suturing.
These photographs will be analyzed to determine the impress ed strai n on the
wound closure and eventually relate this information to wound breaking
strengtji (WBS).

Studies have been completed using a rat m odel which relate b iologic and
pharmocol o gic interventions to WBS . Certain groups were pharmacologically
intervened during the wound healing process. Significant decrease in WBS was
observed in these groups as compared to control groups. Further studies will
include the comparison of tumor bearing group to control groups.



DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT



Pa gp Qfi

PROJECT NUMBER

ZOl RS 10163-02 BEll



PERIOD COVERED

October 1, 1983 to September 30, 1984



TITLE OF PROJECT (80 characters or less Title must lit on one //ne between the borders.)

Magnetoencephalographic Localization of Foci of Neurologic Activity



PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator ) (Name, title, laboratory, and institute aftiliation)



P.O. Smith Visiting Scientist BEIB, DRS



R.F. Bonner
W.S. Friauf
S. Sato
R. Porter
M. Nisenoff



Physicist
Section Chief
Sr. Investigator
Chief
Chief



BEIB, DRS
BEIB, DRS
EB NINCDS
EB NINCDS
NRL



COOPERATING UNITS (il any)

Epilepsy Branch, NINCDS; Naval Research Laboratory



LAB/BRANCH

Biomedical Engineering and Instrumentation Branch



SECTION

Electrical and Electronic Engineering Section



INSTITUTE AND LOCATION

DRS, National Institutes of Health, Bethesda, MD 20205



TOTAL MAN-YEARS:



1.0



PROFESSIONAL:



0.8



OTHER:



0.2



CHECK APPROPRIATE BOX(ES)

K (a) Human subjects
D (a1) Minors
D (a2) Interviews



D (b) Human tissues D (c) Neither



SUMMARY OF WORK (Use standard unreduced type- Do not exceed the space provided.)



A conti nued col 1 abor
SQUID magnetometer t
epileptic patients. C
signal for these disch
the same neurological
the surface of the sea
of the epileptic foe
techniques have been d
aim of producing an
epileptic discharges
scanned using these
associated with a sing
been specified.



ation with the Naval Research Laboratories has enabled a
be used to study inter-ictal spike discharges in
orrelation of the MEG activity and the corresponding EEG
arges permits signal averaging of spikes associated with
event. These measurements allow a magnetic field map at
Ip to be obtained from which a prediction of the source
us can be made. Computer and electronic processing
eveloped to analyze these MEG and EEG signals with the
efficient method of localizing the sources of the
in a selective manner. Several patients have been
techniques. To enhance the collection of MEG data
le spike discharge, a seven channel array detector has



Page 97
ZOl RS 10163-02 BE!

OBJECTIVE: The development of a SQUID magnetic field gradiometer and
methodology for its use to localize the three dimensional coordinates of the
foci of neurologic activity in the brain particularly those associated with
epileptic discharges.

METHODS EMPLOYED: Through collaboration with the Naval Research Laboratory, a
single channel second order magnetic field gradiometer has been used to study
the MEG signals perpendicular to the surface of the scalp arising from spike
discharges in epileptic patients. Simultaneous EEG scalp activity has been
monitored using a full set of electrodes. Both MEG and EEG signals were
recorded for typically 2 hours per session as the SQUID sensor was positioned
across the surface of the scalp. A non-magnetic gantry and bed were designed
and constructed to facilitate this positioning of the sensor with as little
inconvenience to the patient as possible. Correlation of the MEG and EEG
signals was performed off-line using both a computer and a digital processing
oscilloscope. Based on these analyses, real time processing of the MEG and
EEG signal has been instigated.

MAJOR FINDINGS: In trying to localize the source of neurologic activity
associated with an epileptic spike discharge, the major limitation in
producing a magnetic field map required to achieve this goal is the
non-reproducible nature of the neurological event being measured. In fact,
there are two aspects to this non-reproducibi 1 ity: firstly, the signal derived
from any given inter-ictal discharge is variable, due either to the
recruitment of a variable number of neurons cooperating to produce the spike,
or alternatively, to a change in orientation within a neuron grouping. A
second factor is that in many patients there exist multiple sites of
neurological activity each of which elicit an EEG and MEG signal. For these
considerations, and based on findings described below using a single sensor, a
multiple channel array has been specified to permit simultaneous position
measurements of the MEG signal associated with an individual spike discharge.
This array will comprise six 1.5 cm diameter coils arranged in a circle with
another single coil at the center; the spacing of the center coil to any of
the coils arranged in the circle is 3 cm, and the planes and the coils are
arranged on the 10 cm mean radius of the skull. Noise cancellation channels
are also to be provided. This detector is at the limit of current
sensitivities and represents the maximum number of channels to which present
dewar technology can accommodate.

The single channel measurements have been made with the SQUID sensor placed
perpendicular and as close as possible to the scalp. In all cases a set of
EEG electrodes were present and used as markers of position for the SQUID
sensor. A major effort has been to develop a methodology, which is aimed at
reducing the time required to scan a patient, to analyze the data so that
spikes arising from varied locations can be distinguished; this permits signal
averaging techniques to be applied to signals arising from the same location.
Cross-correlation and auto correlation techniques were applied to the MEG and
selected EEG signals using both a mainframe computer and a digital processing
oscilloscope. The main drawback of this type of analysis is that it cannot be
performed in real time and thus the investigator is not able to make
on-the-spot decisions on the most appropriate head scan to pursue. Where
correlation was found to exist, simple multiplication of the MEG and EEG
signals gave essentially the same results in terms of demonstrating
correlation, as well as being performable in real time. A signal processing
module is now being evaluated with this capability; additional functi&n^s



Page 98
ZOl RS 10163-02 BEI

available on-line from this module are (MEG)2/(EEG)2 which gives the ratio of
the power associated with each discharge and thus provides a normalization of
the signals, and (EEG)3 and (MEG)3 which enhance the spike signal to noise
ratio while preserving polarity to permit detection of the spike event. It is
felt these techniques will allow the MEG activity to be measured for each
neural grouping and provide means of normalizing each spike so that signal
averaging can be applied to a unique focus.

PROPOSED COURSE: To compare the results obtained from the signal processing
module with more sophisticated analysis using a mainframe computer and to
provide additional processing where necessary. To evaluate the prediction of
source localization with in-depth cortical electrodes for patients undergoing
surgery and based on these results, to refine the mathematical methods used to
make to make this prediction.

SIGNIFICANCE: The potential of MEG to localize in three dimensions the source
of neurologic discharges noni nvas i vely offers a great advantage over
conventional scalp EEG recording which suffers from the diffusion of scalp
electrical potentials, due to high skull resistance. The localization of
epileptic foci in patients inadequately responding to drug therapy is
important in the evaluation of surgical prospects and the direction of
surgical procedures. The noninvasive localization of coordinates of normal
and abnormal neurologic activity in the brain offers the potential for much
greater understanding of the topography of human brain neurologic processing.



DEPARTMENT OF HEALTH AND HUMAN SERVICES - PUBLIC HEALTH SERVICE
NOTICE OF INTRAMURAL RESEARCH PROJECT



Page 99

PROJECT NUMBER



ZOl RS 101/0-02 BEI



PERIOD COVERED

October 1, 1983 to September 30, 198'f



TITLE OF PROJECT (80 characters or less Title must tit or] one line between the borders j

Biological Applications of a Computer Controlled Analytical Electron Microscope



PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator.) (Name, title, laboratory, and institute atliliation)

R.O. Leapman Visiting Scientist BEIB, DRS

Others:

C.E. Fiori Physical Scientist BEIB, DRS

C.R. Svyyt Physical Scientist BEIB, DRS

K.E. Gorlen Electronic Engineer CSL, DCRT

C.C. Gibson Electronic Engineer BEIB, DCRT

R.L. Ornberg Senior Staff Fellow LCBG, NIADDK



COOPERATING UNITS (if any)

DCRT, NIADDK



LAB/BRANCH

Biomedical Engineering and Instrunentation Branch



SECTION

Electron Beam Imaging and Microspectroscopy Group



INSTITUTE AND LOCATION

DRS, National Institutes of Health, Bethesda, MO 20205

TOTAL MAN-YEARS: I PROFESSIONAL:

2.5 2.5



OTHER:



CHECK APPROPRIATE BOX(ES)

D (a) Human subjects D (b) Human tissues SI (c) Neither

n (a1) Minors
D (a2) Interviews



SUMMARY OF WORK (Use standard unreduced type. Do not exceed the space provided.)

The computer controlled analytical electron microscope developed jointly by

BEIB and CSL, DCRT, provides a unique tool for measuring sub-cellular

elemental distributions with a resolution of some 10 nm. Experiments have

been carried out to test the capabilities of the instrumentation and to

develop further the methodologies for analysis. Nitrogen electron energy loss

images have been recorded from cryofixed pancreas beta and adrenol chromaffin

cells. Calcium and nitrogen maps have been obtained from rapidly frozen and

freeze substituted spinal cord neurons, treated with potassium and sodium

glutamate to produce calcium deposits in their mitochrondria. In these images

it has been found crucial to model the spectral background correctly and a


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Online LibraryNational Institutes of Health (U.S.). Biomedical EAnnual report: National Institutes of Health. Division of Research Services. Biomedical Engineering and Instrumentation Branch (Volume 1984) → online text (page 9 of 13)