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FY 1995 ANNUAL REPORT



Biomedical Engineering and Instrumentation Program

National Center for Research Resources

National Institutes of Health



NATIONAL INSTITUTES OF HEALTH
NIH LIBRARY



MAY I 1996



LBLDG 10, 10 CENTER DR.
BETHESDA, MP 20892-1150



BIOMEDICAL ENGINEERING AND INSTRUMENTATION PROGRAM

NATIONAL CENTER FOR RESEARCH RESOURCES

NATIONAL INSTITUTES OF HEALTH

ANNUAL REPORT FOR FY 1995
Dr. Henry S. Eden, Acting Director



Edited by Bony Bowman, OD, BEIP



BEIP RESEARCH PROJECTS (Z01 RR)



PROJ. NO. TITLE OF PROJECT

10001-27 Pharmacokinetics

1 0034- 1 8 Three-Dimensional Histological Reconstruction

10039- 1 8 Biophysical Instrumentation and Methodology

10097-15 Studies in Cardiovascular Dynamics

10098- 1 5 Laser Instrumentation for Vitreous and
Cardiovascular Microsurgery

10112-15 Analysis of Microcirculatory B lood Flow by
Laser Doppler Scattering

10122-14 Microcomputer Applications for the NIH
Biotechnology Unit (Pilot Plant)

101 62- 1 3 Wound Healing: Biology and Rheology

101 84- 1 2 Physical Chemistry of Biological Macromolecules

10214- 1 1 Photodynamic Therapy

1 0225- 1 1 Processing of High-Resolution Electron Micrographs

10256-09 Mechanical Prosthetic Heart- Valve Tester

10257-09 Analysis of Propagation of Light in Turbid
Biological Tissues

10258-09 Photochemical Inactivation of Virus and Bacteria
in Blood

10259-09 Visual Target-Tracking Ability Assessment System

10272-08 Photometry for Photodynamic Therapy

10276-08 Microdialysis Probe Studies

1 0285-08 Calorimetric Investigation of DNA/Anthracycline
Drug Interactions

10296-08 Experiments with a High-Resolution Field-Emission
STEM

10303-07 Assessment of Scratching in Biliary Cirrhosis
Patients

1 0305-07 CC Image Management System



PRIN. INV. PAGE



R. Dedrick


1


S. Leigh ton


5


M. Lewis


7


R. Chadwick


9


R. Bonner


11


R. Bonner


14


T. Clem


17


T. Talbot


19


M. Lewis


22


P. Smith


26


M. Unser


30


T. Talbot


33


R. Bonner


35


R. Bonner


38


T. Clem


40


V/. Friauf


42


P. Bungay


45


C. Mudd


52


R. Leapman


54


T. Talbot


58


R. Levin


60



TABLE OF CONTENTS (com.)



PROJ. NO. Tm.H OF PROJECT



PRIN. INV. PAGE



1 03 1 3-07 High-Speed Multichannel Spectrophotometer

103 15-07 A Model of Magnetic Stimulation of a Nerve Fiber

1 03 1 8-07 Apple Macintosh U-Based Image Processing
Workstation

10322-07 Data Acquisition System for an Ultrahigh-
Resolution Dedicated STEM

10324-07 In Vitro Hemodynamic Models for Cardiovascular
Studies

1 0327-07 Mass Mapping of Macromolecular Assemblies

1 03 3 1 -06 Microanalysis of Rapidly Frozen Tissue in the
Field-Emission STEM

10337-06 High-Resolution Scintigraphic Imaging Systems

10339-06 Support of Diagnostic Radiology Research Program

10343-06 Polynomial Spline Signal-Processing Techniques

10353-05 Drug Transport in Brain

10358-05 Heat Capacity Effects in Lipids During Unilamellar/
Multilamellar Phase Changes

10359-05 Flash Photolysis of Microsomal P450

1 036 1 -05 Rheology of Sickle Erythrocytes

10362-05 Binding Forces in Receptor-Mediated Cell Adhesion

1 0363-05 Current Dipole Localization Using EEG Data Model

10373-05 Operation of the //iVjvo NMR Research Center

10378-04 Mechanisms of Angioplasty and Atherectomy of
Coronary Stenoses

10380-04 Pathophysiology of Syringomyelia

1 03 8 1 -04 Patient Electronic Monitoring System, Model n

1 03 8 6-04 Calculation of Electrical Activity in Cardiac Tissue

10387-04 A Three-Dimensional Motion Measurement System



W. Friauf

B. Roth

M. Unser

C. Swyt



62
64

67

70



R. Lutz


74


R. Leapman


79


R. Leapman


81


A. Markowitz


83


R. Levin


85


M. Unser


88


P. Morrison


91


CMudd


94


A. Markowitz


96


R. Chadwick


99


A. Eidsatii


101


B. Roth


103


C. Moonen


106


R. Bonner


107


A. Eidsath


110


H. Cascio


112


B. Rotii


114


H. Cascio


117



TABLE OF CONTENTS (cont.)



PROJ. NO. TITLE OF PROJECT

10388-04 3-D NMR Imaging

10394-04 Biological Pulsed Electronic Spin Resonance System

1 0395-04 Digital Differential Themiistor Thermometer

10396-04 Characterization of Frozen-Hydrated Specimens by
EELS

10398-04 Diffusion Tensor Spectroscopy and Imaging

1 0399-03 Development of a Cell Sorter

10403-04 Functional Analysis and Applications to Biomedical
Image Processing

10404-04 Mathematical Methods in Gel Electrophoresis

10405-04 A System to Measure Head Motion Inside a PET
Scanner

10406-04 Development of a Fiber-Optic Gastric pH Sensor

10407-04 Elasticity and Active Force Generation in Cochlear
Outer Hair Cells

1 04 1 0-04 MRI Muscle Dynamometer

1 04 1 3-03 Female Rhesus Monkey Reproductive Physiology
and Behavior Study

10414-03 C-13 MRS Studies of MetaboUc Paths and
Conversion of Ibuprofen Enantiomers

1 04 1 6-03 Mathematical Modeling of Calcium Waves in
Astroglia

1 04 1 8-03 Transport of Macromolecules

1 04 1 9-03 Aluminum in Alzheimer's Disease

10420-03 Thymidylate Synthase Regulation

1 0422-03 Biomedical AppUcations of Optical Low-Coherence
Reflectometry

10424-03 NMR Center Workstations and NMR Center
Internetwork (SPINet)

10425-03 Animal MRI Systems Maintenance, Protocol
Development, Operator Training



PRTN. INV. PAGE



C-N. Chen


119


T. Pohida


121


W. Friauf


123


R. Leapman


125


P. Basser


128


J. Peterson


131


A. Aldroubi


133


A. Aldroubi


136



S. Goldstein 138
J. Peterson 140



R. Chadwick


143


S. Leighton


145


T. Pohida


149


C-N. Chen


151


B. Rotii


153


C. Sung


155


C. Swyt


158


P. Morrison


161



R. Bonner 164

G. Sobering 167

A. Olson 168



ui



TABLE OF CONTENTS (cont.)



PROJ. NO. rm .EOF PROJECT



PRTN. INV. PAGE



1 0426-03 Apple Macintosh Computer Administration at the
NIH In Vivo NMR Research Center

1 0427-03 Development of In Vivo Proton NMR Spectroscopy
and Spectroscopic Imaging

10428-03 Development of the Use of Field Gradients in High-
Resolution NMR Spectroscopy

10429-03 Development of Functional MRI Approaches

10430-03 Functional MR Imaging

1043 1 -03 Development of In Vivo NMR Diffusion
Spectroscopy and Imaging

10445-02 Subcellular Ion Distributions in Acanthamoeba
castellanii

10446-02 Clinical Nitric Oxide Measurement System

10447-02 Aluminum Standards for Alzheimer's Disease
Research

1 0448-02 A Patient Simulator for Hemofiltration Procedures

1 0450-02 The Effect of Temperature Gradients on Calorimetric
Measurements in Fluids

10452-02 Calorimetric Investigation of Protozoa

1 0455-02 Wavelet Transform Applications to Biology

10456-02 New Algorithms for Multimodality Image
Analysis of the Brain

10458-01 Hydrostatic Tissue Clamp

19459-01 A System to Measure Head Motion Inside an
MRI Scanner

10460-0 1 Development of an AOTF Raman Scattering
Microscope

1 046 1 -0 1 MRS Data Processing

1 0462-0 1 Pulse Programming and Data Processing of MRI
on the G.E. Signa System



Y. Shiferaw 169



C. Moonen


170


C. Moonen


172


C. Moonen


174


R. Levin


177


C. Moonen


179


R. Leapman


181


A. Eidsath


183


C. Swyt


185


T. Talbot


187



C. Mudd 189

C. Mudd 191

A. Aldroubi 193

M. Unser 196

S. Leighton 199

S. Goldstein 201

S. Goldstein 204

C-N. Chen 207



C-N. Chen



208



TABLE OF CONTENTS (cont.)



PROJ. NO. TITLE OF PROJECT



PRIN. INV. PAGE



10463-01 Heart-Rate Variability in Endotoxemia

10464-01 Acoustic and Visual Communication in a 4-Tesla
MRI Apparatus

1 0465 -0 1 Fluorescence Analysis of Inter- and Intracellular
pH and Membrane Potential

10466-01 Muscle Cell Electrical Stimulation to Study
Hypertrophic Cardiomyopathy

10467-0 1 Spectrofluorometric Measurement of the Critical
Bilayer Assembly Temperature T*

10470-01 Structure of Clathrin Cages by STEM and Metal
Replication

1 047 1-01 Application of a Post-Column Energy Filter

1 0472-0 1 Low-Dose Energy-Selected Electron Microscopy
With an Omega Filter

10473-01 Positron Emission Mammography Scanner

10474-01 Ganzfeld Stimulator for Clinical Electroretinography



A. Eidsath



P. Smith



P. Smith



T. Pohida



T. Talbot



209



211



214



217



219



R. Leapman 221

R. Leapman 223

R. Leapman 225

A. Markowitz 227

A. Markowitz 230



DEPABTKZHT OF HEXLTB AMD BUH&H SERVICES - PUBLIC HEALTH SERVICE

NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10001-27 BEI



PERIOD COVERED



October 1, 1994 to September 30, 1995



TITLE OF PROJECT (80 ciiaracte

Pharmacokinetics



line betvecn the borders.)



PRINCIPAL INVESTIGATOR IList other professi
institute afCiliation)

Robert L. Dedrick, Ph.D.
Cynthia Sung, Ph.D.
Paul F. Morrison, Ph.D.
Peter M. Bungay, Ph.D.



aJ personnel belo



the Principal Investigator. ) (Name, title, .laboratory, and



Chief

Senior Staff Fellow
Physical Scientist
Chemical Engineer



CHES, BEIP, NCRR

CHES, BEIP, NCRR

CHES, BEIP, NCRR

CHES, BEIP, NCRR



COOPERATING UNITS ^if



ETB, NIMH (J. Hsiao); CNB, NIMH (D. Pickar) ; PB, NCI (F. M. Balis,
D. E. Cole); SNB, NINDS {J. Heiss); University of Rochester Medical
Center (M. Flessner) ; National Naval Medical Center (C. DiGiovanni) ,
Baylor University (S. M. Blaney)



LAB /BRANCH



Biomedical Engineering and Instrumentation Program



Chemical Engineering Section



INSTITUTE AND LOCATION

NCRR, National Institutes of Health, Bethesda, MP 20892



TOTAL STAFF YEARS :

1.0



PROFESSIONAL:

1.0



0.0



CHECK APPROPRIATE BOX (ESI

_ ( a ) Human
subjects

_(al) Minors
_(a2) Interviews



_ ( b ) H\iman
tissues



X _{c) Neither



SUMMARY OF WORK (Use standard unreduced type. Do



exceed the space provided, t



Physiological pharmacokinetic models are developed for the distribution
and disposition of drugs and environmental contaminants. These models
provide a plausible set of equations that can be used to extrapolate
data from experimental animals to humans, and thereby improve
chemotherapy and risk assessment. A pharmacokinetic model developed
for topotecan in the Rhesus monkey provides a basis for design and
analysis of clinical studies. Important features of the model include
reversible opening of the topotecan lactone to an hydroxy acid form,
and transport between the plasma and the cerebrospinal fluid. We have
collaborated in the further development of a clinical protocol for the
administration of AZT into cerebrospinal fluid for the treatment of
AIDS dementia. Collaborative research on intraperitoneal drug
administration has emphasized macromolecules . Work has been extended
on the development of methods using IBZM and SPECT to quantitate D2
receptor densities, affinities, and endogenous dopamine competition for
the binding sites. Analyses based on a pharmacokinetic model for IBZM
suggest that data scatter from SPECT was sufficiently large that D2
receptor density and dopamine content often appeared correlated.
Parameter estimation from PET ligand analysis seems preferable because
of favorable counting statistics attainable with late-generation, high-
efficiency gamma cameras.



PHS 6040 (Rev. 5/92)



ZOl RR 10001-27 BEI

RELEVANT BEIP PROJECTS: 73-159, 89-116, 91-140, 92-131, 93-
103, and 95-104.

OBJECTIVES: To improve and extend mathematical models for the
distribution and disposition of drugs, environmental contaminants,
and endogenous metabolites in animals and humans to:

(1) Account for species differences in drug distribution.

(2) Provide a rational basis for extrapolating toxicity from
experimental animals to humans .

(3) Provide a basis for optimizing chemotherapy, with particular
emphasis on regional drug delivery.

(4) Enable rational transfer of in vitro thermodynamic and
kinetic data to in vivo cases.

METHODS EMPLOYED: Mathematical models are developed from
physicochemical, physiological, and anatomical information and the
principles of chemical-reaction engineering. Resulting ordinary
or partial differential equations are solved analytically or
numerically and compared with experimental data. Uncertainties
are clarified by additional experiments and model modification.

(1) For the treatment of leptomeningeal neoplasia, drugs can be
administered directly into the cerebrospinal fluid (CSF) .
Clinical interest has been enhanced by the development of
pharmacokinetic theory that predicts a large pharmacokinetic
advantage in many cases. We collaborated in studies to
characterize the pharmacokinetics of topotecan, a topoisomerase I
inhibitor and potential anticancer drug. An interesting aspect of
the pharmacology of topotecan is the pH-dependent, reversible ring
opening of the active lactone form to an inactive hydroxy acid
form. Both forms were assayed in preclinical studies in monkeys
receiving injections of the drug intravenously or directly into
the CSF of the ventricles. The data were analyzed with a
physiologically based compartmental model, as well as with a
model-independent method. CSF exposure to the active form of
topotecan was 450 times higher when 0.1 mg was given
intraventricularly than when 4.5 mg was given intravenously. At
the doses tested, no systemic or neurologic toxicity was observed.
The physiologically based compartmental model provides a basis for
extrapolation to human studies.

(2) Research has continued into the development of methods using
IBZM and SPECT to quantitate D2 receptor densities, affinities,
and endogenous metabolite competition for these binding sites. We
used a physiological pharmacokinetic model of IBZM, developed
previously to account for drug metabolism and distribution in rats
and humans, including the accounting of benzamide specific and
non-specific binding in brain tissue. Other investigators using
PET have shown that the percent of D2 receptor bound can be
determined by fitting model equations to the whole tissue binding

PHS e040 (Rev. 5/92)



ZOl RR 10001-27 BEI



data (of raclopride) from experiments in which dopamine is present
or completely suppressed, under the assumption that D2 receptor
levels remain constant in the face of dopamine change . We
endeavored to determine if percent D2 bound could be estimated (1)
when dopamine suppression was not complete, (2) when D2 receptor
levels were not constant (e.g. as with up-regulation associated
with long term exposure to D2-binding drugs) , and (3) SPECT rather
than PET ligands were employed.

We used the following approach: (1) to generate plasma
concentration and D2 and non-D2 brain concentration time histories
from the pharmacokinetic model (for any specific activity of IBZM
ligand) , with preassigned receptor density and affinity, non-
specific binding, and total dopamine concentration parameters; (2)
to scatter the labelled IBZM brain concentration values randomly
(they were sampled every 3 min, according to Poisson counting
statistics variation, given a maximum allowable total radiation
dose of 5mCi) ; and (3) to back-fit only the brain-region portion
of the pharmacokinetic model to these simulated experimental data,
in order to determine mean parameter values and their variances.
Four parameters needed to be determined from data: the non-
specific binding constant, the specific binding affinity of IBZM,
the D2 receptor density, and total dopamine concentration.

Results included the finding that data scatter from SPECT
(mainly arising from Poisson variation secondary to poor
collection efficiency through the collimator) was sufficiently
great that the D2 receptor density and dopamine content parameters
often appeared correlated, and disallowed unique determination of
these parameters. Furthermore, the type of data collection in
SPECT that might resolve this correlation depended strongly upon
the absolute (and experimentally unknown) amount of dopamine
present. These problems suggest that parameter estimation from
SPECT data should now be abandoned in favor of PET ligand
analysis, where much more favorable counting statistics can be
achieved with the use of late-generation, high-efficiency gamma
cameras .

(3) Dementia is commonly associated with accpaired immunodeficiency
syndrome (AIDS) . While the human immunodeficiency virus (HIV)
does not appear to infect neurons directly, cells such as
microglia within the brain may be infected, and this can
apparently lead to central nervous system pathology. Preliminary
clinical studies from France showed that administration of AZT
directly into the CSF was well tolerated in nine patients, and
five of them demonstrated improvement in their symptoms . We are
continuing to collaborate in the design of, and in the development
of the rationale for, a Phase I clinical trial. Calculations
suggest a very large and possibly exploitable pharmacokinetic
advantage resulting from direct administration of AZT into
ventricular CSF, but AZT removal from the CSF is relatively rapid;
ventricular levels, therefore, are probably not representative of
concentrations in the subarachnoid space. The depth of
penetration of AZT into the brain from the CSF is a critical issue
that we have examined in rats both experimentally and
theoretically by means of microdialysis . Efflux from the brain of

PHS £040 (Rev. 5/92)



ZOl RR 10001-27 BEX

brain of rats by a probenecid-inhibited process has led to
incorporation f probenecid in the clinical protocol in an attempt
to improve AZl kinetics in the CSF and to increase the depth of
AZT penetration into the brain. A draft protocol for a Phase I
clinical trial has been prepared, and the stability of AZT in the
implantable pumps proposed for the trial is under investigation.

SIGNIFICANCE: Drugs and other chemicals are tested for effects
in animals and in vitro systems, with the aim of extrapolating the
results to humans. Both the risk associated with environmental
contaminants and the optimization of therapy are at issue.

PROPOSED COURSE: To continue pharmacokinetic modeling, with
consideration of pharmacodynamic and cytokinetic events and drug
interactions. To continue the support of regional procedures and
other measures to overcome drug resistance. To perform research
designed to investigate distribution and metabolism of environ-
mental contaminants, and to find methods for incorporating
pharmacokinetics in models of risk assessment. To investigate
chemical metabolism in vitro, in conjunction with pharmacokinetic
models for quantitative prediction of metabolism in vivo. To

extend distributed models for the description of drug movement
through tissue.

PUBLICATIONS:

Blaney S, Cole DE, Godwin K, Sung C, Poplack DG, Balis FM.
Intrathecal administration of topotecan in nonhuman primates.
Cancer Chemother Pharmacol 1995;36:121-4.

Flessner MF, Dedrick RL. Monoclonal antibody delivery to intra-
peritoneal tiimors in rats: effects of route of administration and
i.p. solution osmolality. Cancer Res 1994;54:4376-84.

Flessner MF, Dedrick RL. Role of the liver in small solute
transport during peritoneal dialysis. J Am Soc Nephrol
1994;5:116-20.

Flessner MF, Dedrick RL. Intraperitoneal chemotherapy. In:
Gokal R, Nolph KD, eds . A textbook of peritoneal dialysis. The
Netherlands: Klewer Academic Publishers, 1994; 769-89.

Sung C, Blaney S, Cole DE, Balis FM, Dedrick RL. A pharmaco-
kinetic model of topotecan clearance from plasma and cerebrospinal
fluid. Cancer Res 1994;54:5118-22.

Bungay PM, Dedrick RL, Fenstermacher JD, Patlak CS, Krindel P.
Estimation of blood sampling errors resulting from metabolism and
solute exchange between plasma and formed elements . J Pharmacol
Toxicol Methods 1994;32:169-75.

Bungay PM, Fenstermacher JD, Krindel P, Dedrick RL, Patlak CS.
Cross-flow plasmapheresis technique for continuous ex vivo plasma
sampling. J Pharmacol Toxicol Methods 1994;32:177-88.

PHS 6040 (Rev. 5/92)



DEPARTHENT OF BEJU^TB AND BOUAN SERVICES - PUBLIC H£ALTB SERVICE

NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10034-18 BEI



PERIOD COVERED

October 1, 1994 to September 30, 1995



TITLE OF PROJECT (80 characters or less. Title



the borders . )



Three-Dimensional Histological Reconstruction



PRINCIPAL INVESTIGATOR (List other professional personnel below the Principal Investigator. } IName,



lahoratory, ^u3d



institute affiliation)

Stephen Leighton, Sc.D.



Mechanical Engineer



MES, BEIP, NCRR



COOPERATING UNITE fif anyl

Marine Biological Laboratory (A. Kuzirian) ; LAS, NINDS (J. Olds)



LAB /BRANCH

Biomedical Engineering and Instrumentation Program



SECTION

Mechanical Engineering Section



INSTITUTE AND LOCATION



NCRR, National Institutes of Health, Bethesda, Maryland 20892



TOTAL STAFF YEARS :

0.1



PROFESSIONAL;

0.1



0.0



CHECK APPROPRIATE BOX ( ES 1



_ ( a ) Human

subjects

_(al) Minors
_(a2) Interviews



_ ( b ) Human
tissues



X _{c) Neither



SUMMARY OF WORK (Use standard unreduced type. Do



exceed the space provided . }



A semiautomatic system for acquiring three-dimensional structural
information about histological material is being developed. The system
should be faster and more reliable than techniques that use serial
sections, although resolution may be limited. In brief, an embedded
tissue block will be fixed relative to a scanning electron microscope
imaging system; the surface of the block will be imaged and the image
stored, and successive slices will be removed by a built-in microtome.
Handling and registration of thin sections will thus be eliminated.
Human and computer pattern recognition will transform the resulting set
of images into a three-dimensional reconstruction. The images of
Hermissenda crassicornis obtained by this technic[ue correlate well with
TEM images of the same tissue.



PHS 6040 (Rev. 5/921



ZOl RR 10034-18 BEI



OBJECTIVES: (1) To facilitate making schematic diagrams of
neural networks. (2) To facility e developmental studies of small
organs and organisms. (3) To do three-dimensional reconstruction
of biological structures.

METHODS EMPLOYED: In order to widen the applicability of Serial
Block Face Imaging (SBFI) , preliminary studies were done with
human tonsillar tissue, both frozen and embedded in epon . Imaging
was done in several modern field-emission scanning electron
microscopes (FESEMs) to determine the resolution limits of the
technique and to assess any other implications of modern FESEM for
SBFI.

MAJOR FINDINGS : The improved FESEMs permit visualization of
structures as small as the trabecular meshwork within some epon-
embedded cells. It is interesting that this structure is
difficult to image with traditional SEM because of its combination
of fine structure and three-dimensional structure. Two major
parts of the SBFI cycle are impacted very favorably by the change
from traditional SEM to FESEM. The time required for oxygen
etching may be greatly reduced, since higher-resolution images do
not require nearly as deep an etch to show the relevant
morphology. In many cases, the metal-coating part of the cycle is
not required at all because the FESEM can be operated at low kV
without charging artifacts. These two improvements mean that the
overall cycle time can be significantly reduced. Frozen tissue
was also imaged successfully, paving the way for rapid examination
of unfixed tissues in three dimensions.

PROPOSED COURSE: We expect to try our system with immunogold-
labeled tissue. We also expect to rearrange an OTOTO staining
procedure originated by Tanaka et al . for use with SBFI. This
project relates to three of BEIP's intramural research
collaborations: infra-red sublimation of ice as a freeze etching
technique (Dr. T. Reese, NINDS) ; hydrostatic tissue clamping (Dr.
C. Collin, NINDS); and "en bloc" removal of soluble protein for
subsequent serial block face imaging (Dr. L. Margolis, NICHD) .



PHS 6040 (Rev. 5/92)



DKPJUlTliUrT or HXALTH AKD HDIUUI SIKVTOS - PDBLIC BKAI.TB lUtVTCl

NOTICE OF INTRAMURAL RESEARCH PROJECT



PROJECT NUMBER



ZOl RR 10039-18 BEI



PERIOD COVERED

October 1, 1994 to September 30, 1995



TITLE OF PROJECT (80



the borders . }



Biophysical Instrumentation and Methodology



PRINCIPAL INVESTIGATOR ILlSt
institute affiliation)

Marc S. Lewis, Ph.D.
Peter J. Basser, Ph.D



professional personnel belou the Principal Inv



Research Chemist
Biomedical Engineer



OD, BE IP, NCRR
MES, BEIP, NCRR



COOPERATING UNITS (if anyl

None



LAB/BRANCH

Biomedical Engineering and Instrumentation Program



Microanalysis Section



INSTITUTE AND LOCATION


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