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Annual report : National Center for Research Resources (Volume 1992 pt.2) online

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San Francisco: San Francisco Press, 1992; 1566-7.

Leapman RD, Hunt JA, Buchanan RA, Andrews SB. Measurement of low
calcium concentrations in cryosectioned cells by parallel-EELS
mapping. Ultramicroscopy (in press).



PHS 6040 (Rev. S/92)



63



raPARnmrT or hbalth jum hdhxii bsrvicss - public exu-th sutvio
NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10303-04 BEI



PERIOD COVERED



October 1, 1991 to September 30, 1992



the borders. )



TITI£ OF PROJECT (80 characters or less. Title must fit on one line .

Assessment of Scratching in Biliary Cirrhosis Patients



PRINCIPAL INVESTIGATOR (List other professional personnel belou the Principal Investigator.! fName, title, laboratory, and institute



jffiJiatian;

Thomas Talbot, M.S.

Joseph Schmitt, Ph.D.

Elijah Walker, M.S.



Mechanical Engineer
Staff Fellow
Section Chief, ACES



BE IP, NCRR
BEIP, NCRR
BE IP, NCRR



COOPERATING UMITS (If any)

LPS, NIDDK (N. Bergasa, E. A. Jones)



LAB/BRANCH



Biomedical Engineering and Instrumentation Program



Applied Clinical Engineering Section



INSTITUTE AND LOCATION

NCRR, National Institutes of Health, Bethesda, Maryland 20892



TOTAL STAFF YEARS:

1.5



PROFESSIONAL:

1.5



0.0



CHECK APPRCS'RIATE BOX(ES)



_(a) Human
subjects

_(al) Minors
(a2) Interviews



_(b) Human
tissues



(c) Neither



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

Patients with primary biliary cirrhosis suffer from severe bouts of
itching, manifested by chronic scratching. In order to evaluate the
efficacy of experimental drugs that may relieve the itching, it is
necessary to quantify the scratching. A piezoelectric foil cemented to
the patient's primary scratching fingernail will transduce mechanical
vibrations generated by the scratching into an electrical signal, which
is applied to the input of a miniature FM transmitter. After the
signal is obtained with an FM receiver, it will be processed by a
custom-designed frequency counter, which in turn is interrogated and
reset periodically by a personal computer. The study will consist of
measurement periods of six to eight hours, both before treatment and
after treatment with specific drugs. Each patient will serve as his or
her own control .



PHS 6040 (Rev. 5/92)



64



ZOl RR 10303-04 BEI

MAJOR FINDINGS: A scoring scheme was devised and implemented
that provides an average scratching activity index per hour. This
index was used in a large double-blind clinical protocol to
determine the viability of Naloxone, an opiate receptor
antagonist, as an ameliorating agent in the treatment of pruritus.
The study, which is now complete, ran for four consecutive 24-hour
periods, with two control (placebo) periods and two Naloxone
periods. Neither the patients nor the investigators were aware of
the contents of the I.V. infusate during the study. The results
clearly demonstrated a statistically significant reduction in
scratching activity while the Naloxone was being infused,
indicating that the drug is effective in ameliorating the pruritus
associated with cholestasis. The results of the study have been
published. In addition, a new clinical protocol is underway,
consisting of a double-blind study designed to investigate
Nalmafene, the oral counterpart of Naloxone. Parallel analysis of
certain underlying circadian rhythms that may unveil imprinted
scratching behavior is also underway. Preliminary indications
imply that scratching may be an independent biorhythm, as well as
a manifestation of a dermal antagonist.

PROPOSED COURSE: Simultaneous recordings of ECG and scratching
are being obtained to investigate the frequency of the biorhythms
that may be associated with scratching.

PUBLICATIONS: Bergasa NV, Talbot TL, Ailing DW, Schmitt JM, et
al . A controlled trial of Naloxone infusions for the pruritus of
chronic cholestasis. Gastroenterology 1992;102:544-9.

Talbot TL, Schmitt JM, Bergasa NV, Jones EA, Walker EC.
Application of piezo film technology for the quantitative
assessment of pruritus. Biomed Instrum Technol 1991;25:400-3.



PHS e040 (Rev. S/92)



65



DSVXllTHUre or BKALTB JUIS BOMJUI (BKVTCSS - PCBLIC BK&I.TB 8SSVIO

NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10305-04 BEI



PERIOD COVERED



October 1, 1991 to September 30, 1992



TITLE OF PROJECT (80 characters or less. Title must fit

CC Image Management System



tJie borders.)



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

Biomedical Engineer BE IP, NCRR



affiliatloni

Ronald L. Levin, Sc.D.



COOPERATING UNITS (if any)

MIS, CC (J. Fov, T. Lewis); DCRT



Biomedical Engineering and Instrumentation Program



Mechanical Engineering Section



INSTITUTE AND LOCATION



NCRR, National Institutes of Health, Bethesda, Maryland 20892



TOTAL STAFF YEARS:

0.1



PROFESS lOHAL:

0.1



0.0



CHECK APPROPRIATE BOX(ES)

_ ( a ) Hiiman
subjects

_(al) Minors
(a2) Interviews



_(b) Hviman
tissues



(c) Neither



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

In order to facilitate the viewing and analysis of biomedical images,
the Clinical Center is in the process of designing and developing an
Image Management System (IMS) to complement the current text-based
Medical Information System (MIS) . This new system will consist of the
following four key components: (1) several different types of medical
image gateways (MIGs) ; (2) an image archival and retrieval system
(lARS) that has an MIS interface; (3) several different types of
workstations (WS) possessing a common biomedical shell; and (4) an
interconnecting communications network. The MIGs will permit digital
radiological images (i.e., MR, CT, PET, etc.), nondigital radiological
images (i.e., plane-film X ray), and nonradiological images (i.e.,
video-microscopic images, EKG tracings, patient monitor information,
etc.) to be converted to a common format, compressed without loss, and
automatically sent to the lARS . The lARS will permit not only the
long-term archiving on optical media of the images coming from the
MIGs, but also the retrieval of multiple modality images to local
workstations in response to queries via the existing MIS data base, the
new IMS data base, or individual departmental data bases. In the
workstation area, we will be developing two or three different types of
biomedical workstations. The key to this series of workstations is
that they would utilize the same biomedical shell (i.e., user
interface) . Application programs for diagnostic imaging, stereotaxic
surgical planning, radiation therapy planning, tumor staging, etc.,
will also be developed.



PHS 6040 (Rev. 5/92)



66



ZOl RR 10305-04 BEI

OBJECTIVES: To facilitate the exchange of medically related
images by permitting images from multiple sources to be accessed
via a single data base and in a single file format, and to
facilitate the manipulation and comparison of medically related
images together with text-based medical records through the use of
a specially designed biomedical workstation.

PROPOSED COURSE: This project is waiting for finalization of
system design parameters and budgetary approval. Phase I (testing
of prototypes of the major system components) will be started in
FY92 through the implementation of the Multimodality Radiological
Image Processing System for the newly created Diagnostic Radiology
Research Program, OD (ZOl RR 10339-03 BEI) .



PBS 6040 (Rev. 5/92)



67



DEPARnmr or bkaltb akd Binuit sxsvicxs - public BSja.Ta bzrvici
NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10307-04 BEI



PERIOD COVERED

October 1, 1991 to September 30, 1992



TITI£ OF PROJECT (SO characters or less. Title must tit

Pulse Oximeter Calibrator



the borders, t



PRINCIPAL INVESTIGATOR (List other profi
affiliation)

Joseph M. Schmitt, Ph.D.

Guanxiong Zhou

Elijah C. Walker, M.S.



ii personnel below the Principal Investigator.} (Name, title, laboratory, and institute



Staff Fellow
Visiting Scientist
Section Chief, ACES



BE IP, NCRR
BE IP, NCRR
BEIP, NCRR



COOPERATING UNITS (if any!

None



LAB/BRANCH

Biomedical Engineering and Instrumentation Program



Applied Clinical Engineering Section



INSTITUTE AND LOCATION

NCRR, National Institutes of Health, Bethesda, Maryland 20892



TOTAL STAFF YEARS:

0.3



PROFESSIONAL:

0.2



0.1



CHECK APPROPRIATE BOX(ES)

_(a) Human
subjects

_(al) Minors
(a2) Interviews



_(b) Human
tissues



(c) Neither



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

Over the last year, we have developed and demonstrated a new method for
simulating the optical signals measured by pulse oximeters . Because it
is easy to implement, the method should enable portable simulators to
be built inexpensively for use in hospitals and factories. The Food
and Drug Administration is now investigating if a simulator based on
our method would be suitable for comparing pulse oximeters as part of a
new standard for apnea monitoring.



PHS 6040 (Rev. S/92)



68



ZOl RR 10307-04 BEI

OBJECTIVES: To design and construct a prototype oximeter
calibrator for use in the Clinical Center. Also, to develop
general mathematical models and calibration techniques for
comparing the performance of oximeters .

METHODS EMPLOYED: Using photon-diffusion theory, we first
analyzed the effect of the primary variables affecting the
calibration of pulse oximeters. Results clearly showed that under
certain physiological conditions, measurement errors can exceed
clinically acceptable bounds. Therefore, there is a need for
better standardization among the various calibration approaches
used by manufacturers of pulse oximeters . To help meet this need,
we have been developing calibration systems that employ
electronically controlled liquid-crystal light valves to simulate
the signals measured by pulse oximeters. By adjusting the
amplitude, waveshape, and frequency of the voltage driving the
valve, its time-dependent transmittance can be made to resemble
that of a blood-perfused finger. Our latest prototype, built
using inexpensive optical components, has been successfully
demonstrated .

SIGNIFICANCE: Many factors affect the accuracy and repeatability
of oxygen saturation values measured by pulse oximeters, including
the volume of blood in the target tissue and the spectral
characteristics and configuration of the light sources in the
optical probe. The results of our photon diffusion analysis have
clarified the role of these factors. The calibration methods that
we are developing can potentially simplify the factory calibration
of pulse oximeters, and form the basis for an inexpensive device
that can be used by clinical and biomedical maintenance personnel
to verify proper operation of pulse oximeters in the hospital.

PROPOSED COURSE: We will continue to encourage the transfer of
this technology to the Food and Drug Administration, which is
working in collaboration with private companies to manufacture a
pulse oximeter calibrator. No further technical development
within the NIH is anticipated.

PUBLICATIONS: Schmitt JM. A simple photon-diffusion analysis
of the effects of multiple scattering on pulse oximetry. IEEE
Trans Biomed Eng 1992;38:1194-1203.

Zhou GX, Schmitt JM, Walker EC. An electro-optic simulator for
pulse oximeters. Med Biol Eng & Comput (in press) .



PHS S040 (Rev. 5/92)



69



DCPUtnoHT or huo-th ako huiuii sxRVias - public hs&lth ssrvio
NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10309-04 BEI



PERIOD COVERED



October 1, 1991 to September 30, 1992



TITLE OF PROJECT (80 characters or less. Title anist fit an one line between the borders.)

Signal Conditioning and Data Acquisition System for Sleep Deprivation Studies



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

Courtney P. Mudd, Ph.D. Biomedical Engineer BE IP, NCRR



COOPERATING UNITS flf any)

CPB, NI^4H (C. Everson)



LAB/BRANCH



Biomedical Engineering and Instrumentation Program



Applied Clinical Engineering Section



INSTITUTE AND LOCATION



NCRR, National Institutes of Health, Bethesda, Maryland 20892



TOTAL STAFF YEARS:

0.2



PROFESSIONAL:

0.2



0.0



CHECK APPROPRIATE BOX(ESI

_(a) Human
subjects

_(al) Minors
(a2) Interviews



_(b) Human
tissues



(c) Neither



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

An AT-type microcomputer with a resident 16-channel, 12-bit A/D board
is used to measure and store signals from small (0.5 mm dia . x 3 mm
long), fast (20 msec), glass-encapsulated thermistors. The calibration
values for each thermistor are stored in a separate calibration file
and are loaded into the program when the program is started. A
thermistor bridge circuit accommodates a tolerance of ±20% in the
nominal thermistor resistance, and covers a range of 25° to 45°C with
0.01°C resolution. Custom software controls the sample acquisition
rate, filtering linearization, calibration, and storage of the signals.
The A/D card runs in a "background" mode for 30-second intervals, with
the data transferred directly to a specified memory location. This
mode of operation frees the CPU for processing the previous interval's
data and allows uninterrupted, or continuous, data acquisition. After
the first cycle, the memory location is switched and another cycle is
started. The program then downloads the 16-channel data from the
previous memory location and determines the resistance of each
thermistor from the voltage readings. From this resistance and the
calibration values, the temperature of each thermistor is calculated.
The "background" operation also allows updating or changing the
calibration values (new thermistor) or relocating the thermistor
(channel change) without interrupting the data acquisition.



PHS 6040 (Rev. 5/92)



70



ZOl RR 10309-04 BEI

OBJECTIVES: The processing and acquisition system have now been
in operation for six months. During this evaluation period, we
have determined that the thermistor measurement system has an
accuracy of ±0.02°C with a resolution of 0.01°C. The transmitter
system, which comes with no calibration or sensitivity
information, has a resolution of 0.05°C, but an accuracy of only
±0.2°C. The source of this error was traced to the water bath
calibration scheme used to measure the sensitivity of the
transmitters .

SIGNIFICANCE: The operation of this continuous data acquisition
system will allow uninterrupted, long-term investigations into the
interdependence of diet and sleep. Preliminary studies have shown
a definite relationship between brain temperature and sleep
deprivation. An accurate system for measuring both the brain
temperature and sleep state (vigilance) is indispensable for
investigating this effect. Our brain temperature accuracy of
±0 . 02°C represents approximately a threefold improvement over the
present system.

PROPOSED COURSE: The data acquisition software has been
developed to handle a wide variety of anticipated errors without
operator intervention. Since the data acquisition is continuous
(24 hr/day) , the software is designed to allow the computer to
recover from a power interruption, determine where it should be in
the data acquisition cycle, and restart the program at the correct
time in the data acquisition cycle. We have also incorporated a
feature that allows the operator to select certain epochs for
complete (unprocessed) data download to a floppy disk for Fourier
analysis of the fast signals (EEGs and EMGs) . An automated,
computer-controlled transmitter calibration system has been
developed that has reduced the transmitter temperature error to
±0.05°C.



PHS 6040 (Rev. S/92)



71



raFARnan or bkalth md bdham sxkvices - public bbaltb sbrvici
NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10310-04 BEX



PERIOD COVERED



October 1, 1991 to September 30, 1992



TITLE OF PROJECT (BO characters or less. Title must tit o/i one line betueen the ttorders.)

Microcalorimeter Measurements of DNA-Protein Interactions



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

Courtney P. Mudd, Ph.D.



Biomedical Engineer



BE IP, NCRR



COOPERATING UNITS (if any)

LMB, NIDDK (P. Ross); FCRF, NCI (Y. Tekeda) ; IR CH, NHLBI (R. Berqer)



LAB/BRANCH

Biomedical Engineering and Instrumentation Program



Applied Clinical Engineering Section



INSTITUTE AND LOCATION



NCRR, National Institutes of Health, Bethesda, Maryland 20892



TOTAL STAFF YEARS:

0.1



PROT"ESSIONAL:

0.1



0.0



CHECK APPROPRIATE BOX(ES)

_ ( a ) Hiaman
subjects

_(al) Minors
(a2) Interviews



_(b) Human
tissues



(c) Neither



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

The use of various proteins to modify the human immune system response
is of intense interest in the areas of organ transplants, AIDS, and
chemotherapy. At the NCI, several new proteins have been developed for
this purpose. At present, these proteins are available only in small
amounts. By mixing these proteins with carefully constructed molecules
of DNA and measuring the enthalpy, the protein-DNA bond interactions
can be determined. Investigators at the NCI and NIDDK consulted the
BEIP about measuring the heats of these small samples. We recommended
using our tantalum stopped-flow microcalorimeter, which has the
capability of measuring heats of 10 microjoules or less in 80-
microliter samples. The first experiments showed that we could measure
heats in the range of 5 microjoules with a standard error of less than
0.5 microjoules. We have now completed the preliminary study of this
protein with two different DNA hosts at 25° and 37°C. Using the
tantalum stopped-flow microcalorimeter, we were able to measure a
binding heat difference when one base pair on the DNA host was changed.
Results show that the enthalpy is very low, which indicates that the
binding is almost exclusively entropy-driven.



PHS 6040 (Rev. S/92)



72



ZOl RR 10310-04 BEX

OBJECTIVES: To reduce the priming volume from 1 ml to
approximately 0.2 ml in order to further conserve reagents, and to
provide a means of automatic loading for unattended operation. We
have also found that part of the flow artifact is due to the
pressure sensitivity of the sensors we use to detect the heat
flow. The new instrument will incorporate a low-stress mounting
system with no static pressure on the sensors.

SIGNIFICANCE: In studying these interactions, very often we
change only one base pair in each experiment . Even a reasonably
small DNA molecule can represent 30 to 40 experiments to study the
protein's reactions. Automatic loading would allow unattended
operation during nonworking hours. The reduced priming volume
will conserve expensive reagents ($4,000 to $5,000 per experiment)
by reducing the number of "lost" runs at the buffer/reagent flow
interface. The reduction of the pressure-induced flow artifact
will increase the usable resolution of the measurement. This is
especially important since the measured heats are very low (10 to
20 microjoules) .

PROPOSED COURSE: We have identified several rotary valves which
can be computer-interfaced to sequence loading and running of the
calorimeter. If we change the inlet lines to the calorimeter from
1.5 mm ID to 0.5 mm ID, the priming volume can be reduced by a
factor of 9. The pre-equilibrator in the calorimeter must be
redesigned, however, to ensure that the reagents are in thermal
equilibrium with core temperature when they reach the mixer. We
plan to use small-bore (0.5 mm ID) tantalum tubing for the inlet
tubes to reduce the priming volume to approximately 200 micro-
liters (vs. 1 ml in the old design) . To reduce the pressure-
induced flow artifact, special spacers will be used to standoff
the flow tube from the sensors by 25 microns. The 25-micron space
will be filled with heat sink compound to conduct the heat from
the reagent tube to the sensors. The smaller inlet tubing will
require a redesigning of the mixing chamber.



PHS 6040 (Rev. S/92)

73



DSPJUtTiOVT or BKXI.TB HMD BUHAI SUtVICIS - PUBLIC HXXI.TH SmVICX

NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT KUMBER



ZOl RR 10313-04 BEI



PERIOD COVERED

October 1, 1991 to September 30, 1992



TITLE OF PROJECT (80 characters or less. Title must fit on one line i

High-Speed Multichannel Spectrophotometer



the borders. 1



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

Walter S. Friauf, MEE Section Chief EEES, BEIP, NCRR

Paul D. Smith, Ph.D. Physicist EEES, BEIP, NCRR

John Cole, MSEE Electrical Engineer EEES, BEIP, NCRR



COOPERATING UNITS (If any)

LCB, NHLBI (R. Hendler) ; CSL, DCRT (H. Frederickson)



Biomedical Engineering and Instrumentation Program



Electrical and Electronic Engineering Section



INSTITUTE AND LOCATION



NCRR, National Institutes of Health, Bethesda, Maryland 20892



TOTAL STAFF YEARS:

1.5



PROFESSIONAL:

1.5



0.0



CHECK APPROPRIATE BOX(ES)



_(a) Human
subjects

_(al) Minors
(a2) Interviews



_(b) Human
tissues



(c) Neither



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

A number of commercial multichannel spectrophotometers using
charge-coupled devices have recently been developed for general use in
biomedical research. We have explored the possibility of improving
both the speed and the accuracy of such instruments by exploiting other
new devices .



PHS 6040 (Rev. 5/92)



74



ZOl RR 10313-04 BEI

OBJECTIVES: To develop a 100-channel spectrophotometer capable
of sampling all channels at a maximum rate of 100,000 samples per
second with 12-bit resolution.

METHODS EMPLOYED: A commercial spectrophotometer will disperse
the light to two 50-element photodiode arrays. Each channel will
integrate the signal between sample times, digitize it, and store
it in a first-in, first-out register prior to digital multiplexing
for transmission to a computer. The computer will provide full
control over the sampling program, as well as over such
experimental parameters as flow and flash photolysis; it will also
handle all of the processing and permanent storage, will display
data, and will perform various other functions.

SIGNIFICANCE: Achievement of the proposed specifications will
open up a variety of new applications. The increased temporal
resolution will permit investigation of early events in
biochemical reaction kinetics that have been impossible to measure
before. The ability to follow these processes with high accuracy
and at multiple wavelengths enables investigators to track
individual components within a complex reaction simultaneously.

PROPOSED COURSE: Design and construction are complete, and the
instrument is in regular use. It is very close to meeting all
original specifications, but additional testing and evaluation are
still needed. We are exploring the possibility of cooling the
diode arrays, adding a programmable offset to each channel, and
increasing the gain to provide improved resolution. We are also
looking into the possible application of image intensifiers to
extend the short wave length response of the instrument. Other
system components (such as the measuring light source) will be
stabilized more tightly, and other optical refinments will be
made .

An invention report has been filed.



PHS 6M0 (Rev. 5/92)



DSVARnmrT or b>ju.tb akd Bmuii sxnvicis



PUBLIC BKJU.TB StKVZCM



NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10314-04 BEI



PERIOD COVERED



October 1, 1991 to September 30, 1992



TITLE OF PROJECT (80 char



line between the borders.)



Pulsed Photodynamic Therapy



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



Walter S. Friauf, MEE
John W. Cole, MSEE



Section Chief
Electrical Engineer



EEES, BE IP, NCRR
EEES, BE IP, NCRR



COOPERATING UNITS (if any)

ROB, DCT, NCI (A. Russo)



LAB/BRANCH



Biomedical Engineering and Instrumentation Program


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Online LibraryNational Center for Research Resources (U.S.)Annual report : National Center for Research Resources (Volume 1992 pt.2) → online text (page 7 of 19)