NMR in Living Systems

405 Pages·1986·23.32 MB·English

by  Edwin D. Becker (auth.), Giulio Ceccarelli (eds.)

NMR in Living Systems
NATO ASI Series
Advanced Science Institutes Series
A series presenting the results of activities sponsored by the NATO Science Committee,
which aims at the dissemination of advanced scientific and technological knowledge,
with a view to strengthening links between scientific communities.
The series is published by an international board of publishers in conjunction with the
NATO Scientific Affairs Division
A Life Sciences Plenum Publishing Corporation
B Physics London and New York
C Mathematical D. Reidel Publishing Company
and Physical Sciences Dordrecht, Boston, Lancaster and Tokyo
D Behavioural and Social Sciences Martinus Nijhoff Publishers
E Engineering and The Hague, Boston and Lancaster
Materials Sciences
F Computer and Systems Sciences Springer-Verlag
G Ecological Sciences Berlin, Heidelberg, New York and Tokyo
Series C: Mathematical and Physical Sciences Vol. 164
NMR in Living Systems
edited by
T. Axenrod
Department of Chemistry,
City College of the City University of New York, U.SA
and
G. Ceccarelli
Institute of Physical Chemistry,
University of Pisa, Italy
D. Reidel Publishing Company
Dordrecht / Bo~ton / Lancaster / Tokyo
Published in cooperation with NATO Scientific Affairs Division
Proceedings of the NATO Advanced Study Institute on
NMR in Living Systems .
Altavilla Milicia (Sicily). Italy
August 26-September 7. 1984
Library of Congress Cataloging in Publication Data
NATO Advanced Study Institute on NMR in Living Systems
(1984) : Altavilla Milicia, Italy)
NMR in living systems.
(NATO ASI series. Series C, Mathematical and physical sciences; vol. 164)
"Proceedings of the NATO Advanced Study Institute on NMR in Living Systems, Altavilla
Milicia, Sicily, Italy, August-September 1984" - T.p. verso.
"Published in cooperation with NATO Scientific Affairs Division."
Includes index.
1. Nuclear magnetic resonance - Congresses. 2. Biology - Technique - Congresses.
I. Axenrod, T. II. Ceccarelli, G. (Giulio) III. Title. IV. Series: NATO ASI series. C,
Mathematical and physical sciences; no. 164.
QH324.9.N8N38 1984 574'.028 85-30044
ISBN-13: 978-94-010-8535-9 e-ISBN-13: 978-94-009-4580-7
001: 10.1007/978-94-009-4580-7
Published by D. Reidel Publishing Company
PO. Box 17, 3300 AA Dordrecht, Holland
Sold and distributed in the U.SA and Canada
by Kluwer Academic Publishers,
190 Old Derby Street, Hingham, MA 02043, USA.
In all other countries, sold and distributed
by Kluwer Academic Publishers Group,
PO. Box 322, 3300 AH Dordrecht, Holland
D. Reidel Publishing Company is a member of the Kluwer Academic Publishers Group
All Rights Reserved
© 1986 by D. Reidel Publishing Company, Dordrecht, Holland.
Softcover reprint of the hardcover 1s t edition 1986
No part of the material protected by this copyright notice may be reproduced or utilized
in any form or by any means, electronic or mechanical, including photocopying, recording
or by any information storage and retrieval system, without written permission from the
copyright owner.
TABLE OF CONTENTS
PREFACE
AN OVERVIEW OF BIOLOGICAL APPLICATIONS OF NMR
c.L. Fisk and E.D. Becker 1
THEORETICAL BACKGROUND TO HIGH RESOLUTION NMR
PARAMETERS AND NUCLEAR SHIELDING CALCULATIONS
G. A Webb 19
AN INTRODUCTION TO NMR RELAXATION MECHANISMS
E.D. Becker and c.L. Fisk 39
SOME CALCULATIONS OF NUCLEAR SPIN-SPIN COUPLINGS
G.A Webb 53
TWO-DIMENSIONAL NMR SPECTROSCOPY
ABu ~
NMR DATA PROCESSING IN COMPUTERS
D. Ziessow 95
THE PHYSICAL BASIS OF NMR TOMOGRAPHY
F. De Luca, B.c. De Simone, B. Maravig1ia,
R. Campanella and C. Casieri 109
THE SENSmVITY OF THE NMR IMAGING EXPERIMENT
D.1. Hoult 117
THE USE OF MODELS IN THE INTERPRETATION OF NMR IMAGES
A. Rescigno and C.C. Duncan 123
CHEMICAL SHIFT IMAGING
D. Shaw 157
MEDICAL ASPECTS OF MAGNETIC RESONANCE
L.D. Hall and W.A Stewart 169
MR-IMAGING AND SPECTROSCOPY OFFERING NEW
POSSIBILITIES IN MEDICAL DIAGNOSES
A Ganssen 177
COST AND A V AILABLITY OF COMMERCIAL NMR EQUIPMENT; AND
REQUIREMENTS FOR HOUSING, INSTALLATION AND OPERATION
L.D. Hiill 193
vi TABLE OF CONTENTS
PRACTICAL ASPECTS OF IN-VITRO AND IN-VNO T1 AND T2
MEASUREMENTS
c.A. Boicelli and A.M. Baldassarri 199
CONS1RUCTION OF A COMBINED rnGH RESOLUTION NMR
SPEC1ROMETER - TOMOGRAPH
L.D. Hall, H.Chow, S. Luck, T. Marcus, C.Neale, B. Powell,
J. Sallos, S. Sukurnar, L. Talagala, and V. Rajanayagarn 217
GATHERING METABOLIC INFORMATION USING 13C AND 1H rnGH
RESOLUTION SPEC1RA OF LIVING SYSTEMS
J. R Alger 231
NON-INVASIVE LOCALIZED VOLUME SPEC1ROSCOPY OF ANIMALS:
PROSPECTS FROM THE VIEWPOINT OF THE rnGH RESOLUTION
SPEC1ROSCOPIST
J.R Alger 265
NMR METHODS FOR MEASURING CATION CONCENTRATIONS IN
BIOLOGICAL SYSTEMS
J.Feeney 279
NMR SPEC1ROSCOPY OF IN1RACELLULAR SODIUM IONS IN LIVING
CELLS
RK. Gupta 291
APPLICATIONS OF CARBON-13 AND SODIUM-23 NMR IN THE STUDY
OF PLANTS, ANIMAL, AND HUMAN CELLS
L. O. Sillerud, J.W. Heyser, C.H. Han and M.W. Bitensky 309
NMR MEASUREMENT OF IN1RACELLULAR FREE MAGNESIUM
IONS IN LNING CELLS
RK.G~ta 3~
NMR STUDIES OF DRUG RECEPTOR COMPLEXES: ANTIFOLATE
DRUGS BINDING TO DIHYDROFOLATE REDUCTASE
J.Feeney 347
NON-MEDICAL APPLICATIONS OF NMR IMAGING
L.D. Hall, J. Lee, V. Rajanayagarn and L. Talagala 367
OTHER METHODS FOR IMAGING THE INTACT HUMAN BODY
L.D. Hall 377
HOW TO COPE WITH THE LITERATURE OF NMR OF LIVING SYSTEMS
L.D. Hall and W.A Stewart 385
LIST OF PARTICIPANTS 391
INDEX 403
PREFACE
In the four decades since its discovery nuclear magnetic resonance (NMR) has
become an indispensable tool for obtaining chemical information often.inaccessible by other
methods. With the development of instruments of increasingly higher magnetic field
strengths, the integration of powerful computers and the availability of an expanding array
of flexible software new applications and developments have proliferated rapidly. Among
the more exciting new advances is the use of NMR spectroscopy to probe biological
systems.
The last ten years have witnessed tremendous progress in the development of new
NMR imaging and spectroscopic techniques for research and diagnostic applications. The
ability to investigate metabolic processes and anatomical structure of intact biological
systems under conditions that are totally non-destructive and non-invasive clearly provides
much of the impetus for the intense activity that has been generated in the fields of
medicine, radiology and the allied basic sciences. Significant advances have been made in
this brief period: Whole-body proton NMR imaging today provides anatomical definition of
normal and abnormal tissue with a contrast and detection sensitivity often superior to those
of X-ray computed tomography and other competing imaging methods. Biochemical
pathways, using NMR spectroscopy of protons, carbon-13 and phosphorus-31 nuclei in
live animals and man can readily be followed by surface-coil methods to detect metabolites
in localized regions. Indicative of the importance and widespread acceptance of these
techniques is the explosive growth that the NMR literature is experiencing. This augers
well for the future.
NMR as a probe in biological systems is by its very nature an interdisciplinary
effort and its continued advancement depends on a combination of expertise drawn from
many areas. These range from the basic physical and biomedical sciences through
engineering and computer technology. The contents of this volume are taken in large part
from the lectures presented at the NATO Advanced Study Institute on "NMR in Living
Systems" held in Altavilla Milicia (Sicily), Italy during September 1984. One of the
objectives of the Institute, and of this volume, was to bring together individuals from the
different fields who could contribute to an authoritative over-all review of the present state-
of-the-art.
In view of the range of interests and levels of NMR experience brought to the
Institute by the participants, the program was designed to impart an in-depth knowledge of
basic theory essential to the later treatment of more advanced techniques and specialized
applications which are at the frontiers of the field today. The basic concepts including the
resonance phenomenon, Fourier transform methods, relaxation mechanisms, spin-spin
coupling, chemical shift spectroscopy, two dimensional NMR, computer data processing
and instrument design were presented in the introductory phases of the program. With this
as fundamental background, the various methods of obtaining and interpreting images,
measuring cation concentrations in cells and following metabolic processes by topical NMR
methods were ,then examined. The power, versatility and limitations of each of these
methods were considered in relation to complementary methods presently available. Future
VB
viii PREFACE
research needs were explored and strategies for coping with the burgeoning literature were
outlined.
Grateful acknowledgment is made to the NATO Scientific Affairs Division for the
generous support of the Advanced Study Institute. Special thanks are due to Professor
Mariella Brai and Dr. Mario Valenza whose handling of many of the organizational details
greatly facilitated the smooth operation of the Institute. Finally, we take this opportunity to
express our appreciation to the lecturers for their advice and assistance in planning the
program and for their cooperation and contributions in producing this volume.
Theodore Axenrod
Giulio Ceccarelli
New York, N.Y. (USA)
Pisa (Italy)
December 1984
AN OVERVIEW OF BIOLOGICAL APPLICATIONS OF NMR
Cherie L. Fisk and Edwin D. Becker
National Institutes of Health
Bethesda, Maryland 20205, USA
ABSTRACT. Since its discovery in 1946, NMR has developed to one of
the most widely used tools in chemistry and is rapidly becoming an
essential technique in biology and medicine. In this introductory
chapter the use of NMR in biology and biochemistry is traced from
early studies of small molecules of biological interest, through the
study in vitro of biopolymers and cell constituents, to the current
applications of in vivo spectroscopy and imaging. The development of
improved instruments and introduction of new methods that are essen-
tial to current uses are emphasized.
1. INTRODUCTION
The last few years have seen an explosive growth in the application
of nuclear magnetic resonance (NMR) to the study of living systems,
ranging from cells in tissue culture, through perfused organs to
intact animals and human beings. Increasingly, NMR data provide
detailed insights into metabolic processes, and the use of NMR
imaging already rivals or surpasses other imaging modalities, such as
x-ray, in its capacity to define anatomical features in humans and to
serve as a leading diagnostic tool. Some biologists and medical
practitioners view NMR as a new technique since it has only recently
made an impact in their fields. But NMR was discovered nearly 40
years ago (i), and in these four decades has moved gradually from a
phenomenon of interest to physicists to an essential tool in chemis-
try, biochemistry and now biology and medicine.
To put the current uses of NMR in perspective, we first review
briefly the origins of the method and its early applications to
chemistry and biochemistry, then trace the extensions of its use as
instruments were improved and new techniques developed. Finally, we
comment on .the present status and probable future developments in the
field.
T. Axenrod and G. Ceccarelli (eds.), NMR ill Living System" 1-17.
2 C. L. FISK AND E. D. BECKER
2. PHYSICAL BASIS OF NMR
NMR arises from the interactions between the magnetic moments of
atomic nuclei and strong magnetic fields imposed in the laboratory.
We shall not provide a detailed account of NMR theory here, since
such developments are available in a number of textbooks (1), but we
shall summarize the important results and equations. Some features
of NMR spectra can be understood only by the use of quantum mechan-
ics, while others can equally well be explained in classical terms.
Both classical and quantum mechanical approaches lead to the funda-
mental equation of NMR (first derived classically by Larmor in
another connection):
(1)
where Vo is the resonance frequency; y, the magnetogyric ratio, is a
property of the particular nuclide being studied (B-1, P-31, etc.);
and B is the magnetic field applied to the sample. In the classical
pictu~e of NMR the nuclear magnetic moment can be pictured as pre-
cessing, like a spinning top, about the magnetic field at the fre-
quency v 0 as illustrated in Figure 1.
Figure 1. Precession
(at the Larmor frequen-
cy, v 0) of a magnetic
moment, ~, about a fixed
magnetic field, Bo. For
detection of the NMR
signal, a radio-
frequency field, Bl ,
(rotating in the xy
plane also at the Larmor
frequency) is intro-
duced. Interaction
between B and ~ (reson-
--Eil::7-"- Y
ance) proAuces a signal
in the spectrometer.
It
In the first few years after the discovery of NMR in 1946 major
attention was focussed on obtaining accurate values of Y for various
nuclei, in understanding the interactions between the nuclear magnets
and the radio-frequency waves used to study their resonance proper-
ties, and in~elucidating the mechanisms by which nuclei relax back to