Magnetic Resonance in Nephrourology: Clinical and Experimental Applications

160 Pages·1993·6.1 MB·English

by  W. E. Hull (auth.)

Sigmund Pomer William E. Hull (Eds.)
Magnetic Resonance
in N ephrourology
Clinical and Experimental Applications
With 77 Figures and 7 Tables
Springer-Verlag
Berlin Heidelberg New York
London Paris Tokyo
Hong Kong Barcelona
Budapest
PD Dr. med. Sigmund Pomer
Chirurgische UniversiHitsklinik
Abteilung Urologie und Poliklinik
1m Neuenheimer Feld 110
D-69120 Heidelberg, FRG
William E. Hull, PhD
German Cancer Research Center
Central Spectroscopy Department
1m Neuenheimer Feld 280
D-69120 Heidelberg, FRG
ISBN-13: 978-3-642-78068-4
Library of Congress Cataloging-in-Publication Data. Magnetic resonance in nephrourology: clinical and
experimental applications/S. Pomer, W.E. Hull (eds.). p. cm. Includes index.
ISBN-13: 978-3·642·78068-4 e-ISBN-13: 978-3·642· 78066'{)
DOl: 1O.lO07/978-3·642·78066'{) 1. Urinary organs-Magnetic resonance imaging. 2. Kidneys-
Magnetic resonance imaging. 3. Kidneys-Cancer-Diagnosis. 4. Organ Preservation. I. Pomer, S.
(Sigmund) II. Hull, W. E. (William E.) [DNLM: 1. Nuclear Magnetic Resonance. 2. Kidney-physiology.
3. Kidney Neoplasms-physiopathaology. WJ 301 M196 1993) RC874.M34 1993 616.6'07548-dc20
DNLMIDLC for Library of Congress 93-9946 CIP
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is
concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting,
reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or
parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in
its current version, and permission for use must always be obtained from Springer·Veriag. Violations are
liable for prosecution under the German Copyright Law.
© Springer·Verlag Berlin Heidelberg 1993
So ftcover reprint of the hardcover 1st edition 1993
The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply,
even in the absence of a specific statement, that such names are exempt from the relevant protective laws and
regulations and therefore free for general use.
Product liability: The publishers cannot guarantee the accuracy of any information about dosage and
application contained in this book. In every individual case the user must check such information by
consulting the relevant literature.
Typesetting: Best-set Typesetter Ltd., Hong Kong
21/3130-5 4 3 2 1 0 - Printed on acid· free paper
Contents
Magnetic Resonance Spectroscopy and Tumor Cell Metabolism
Introduction to Magnetic Resonance and Its Possible Applications
in Nephrourology: High-Field Spectroscopic Characterization
of Renal Cell Carcinoma
W.E. Hull..................................................... 3
31p Magnetic Resonance Studies of Cytokine-Induced Alterations
in Tumor Cells Transplanted into Syngeneic Mice
F. Podo, G. Carpinelli, E. Proietti, and F. Belardelli ................ 14
13C and IH Magnetic Resonance Studies
of Normal and Neoplastic Brain Cells
D. Leibfritz, A. Brand, and C. Richter-Landsberg 25
Magnetic Resonance Spectroscopic Evaluation of the Effects
of High-Energy Shock Waves
Administered to a Human Kidney Cancer Xenograft
A. Heerschap, G.A.H.J. Smits, H.J. van den Boogert,
G.O.N. Oosterhof, F.M.J. Debruyne, J.H.J. Ruijs, and
J.A. Schalken . ........ ................. ....... ........ ...... ... 34
Magnetic Resonance and Kidney Function
31p and IH Magnetic Resonance of the Kidney:
From Experiments in Animals to Applications in Humans
F. Terrier, F. Lazeyras, F. Frey, E. Scott, A. Montandon, and
P. Vock ....................................................... 43
In Vivo 1'T MR Spectroscopy in the Study of Organic Acid Excretion
by the Rat Kidney
U. Ammer and H.P. Juretschke .................................. 61
VI Contents
Magnetic Resonance Evaluation
of Experimental Renal Vein Thrombosis
D. Uhlenbrock ........... " .................... " . . . ... ...... .. 73
Magnetic Resonance and Organ Viability
The Role of Magnetic Resonance in Cryopreservation of Tissues
D.E. Pegg . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 85
Image-Guided Volume-Selective Magnetic Resonance Spectroscopy
and Relaxometry: Application to the Porcine Kidney
Perfused with Perfluorocarbons
G. Schnur . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 93
Diffusion Magnetic Resonance Microscopy of Kidney Preservation
M. Neeman, L.J. Gibel, S.M. Smith, A. Hartford, W. Sterling, and
L.O. Sillerud. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 103
Magnetic Resonance Microscopy of the Mouse Kidney
H.-M. Cheng, L. Garrido, E. Brown, and J.B. Aguayo .............. 109
High-Field 31p Magnetic Resonance Studies
for Evaluating Kidney Viability
S. Pomer and W.E. Hull ................... " .................... 115
Clinical Magnetic Resonance
Overview of Clinical 31p Magnetic Resonance Spectroscopy
Investigations and Applications
for Renal Transplant Viability Assessment
P.N. Bretan, Jr. ................................................ 133
RARE Magnetic Resonance Urography in the Diagnosis
of Upper Urinary Tract Abnormalities in Children
G. Sigmund, B. Stoever, L.B. Zimmerhackl, A. Frankenschmidt,
E. Nitzsche, J.U. Leititis, F.E. Struwe, and J. Hennig ............... 145
Magnetic Resonance Imaging of Solid Renal Masses
T. Roeren, G.M. Richter, and V. Ihle ................ " ........... 153
List of Contributors
Addresses are given at the beginning of the respective contribution.
Aguayo, J.B. 109 Oosterhof, G.O.N. 34
Ammer, U. 61 Pegg, D.E. 85
Belardelli, F. 14 Podo, F. 14
Brand, A. 25 Pomer, S. 115
Bretan, Jr., P.N. 133 Proietti, E. 14
Brown, E. 109 Richter, G.M. 153
Carpinelli, G. 14 Richter-Landsberg, C. 25
Cheng, H.-M. 109 Roeren, T. 153
Debruyne, F.M.J. 34 Ruijs, J.H.J. 34
Frankenschmidt, A. 145 Schalken, J.A. 34
Frey, F. 43 Schnur, G. 93
Garrido, L. 109 Scott, E. 43
Gibel, L.J. 103 Sigmund, G. 145
Hartford, A. 103 Sillerud, L.a. 103
Heerschap, A. 34 Smith, S.M. 103
Hennig, J. 145 Smits, G.A.H.J. 34
Hull, W.E. 3, 115 Sterling, W. 103
Ihle, V. 153 Stoever, B. 145
Juretschke, H.P. 61 Struwe, F.E. 145
Lazeyras, F. 43 Terrier, F. 43
Leibfritz, D. 25 Uhlenbrock, D. 73
Leititis, J.U. 145 van den Boogert, H.J. 34
Montandon, A. 43 Vock, P. 43
Neeman, M. 103 Zimmerhackl, L.B. 145
Nitzsche, E. 145
Magnetic Resonance Spectroscopy and
Tumor Cell Metabolism
Introduction to Magnetic Resonance
and Its Possible Applications in Nephrourology:
High-Field Spectroscopic Characterization
of Renal Cell Carcinoma
W.E. Hull1
Introduction
The purpose of this introductory chapter is to provide some basic information
regarding the fundamentals of magnetic resonance (MR) for those readers
who are less familiar with the technique. Emphasis here is on MR spectro
scopy and its possible applications in research and clinical practice, hope
fully stimulating the reader to look more closely at the various topics
covered by the contributors to this volume. Finally, some applications of
high-field 13e and 31p MR spectroscopy in the area of renal cell carcinoma
are briefly illustrated.
The Magnetic Resonance Phenomenon
Many natural nonradioactive isotopes have a nuclear spin (a magnetic
moment) and can be induced to give radiofrequency MR signals in a strong,
applied magnetic field (Bo). Important isotopes for biological MR appli
cations re listed in Table 1 along with their abundance, resonance frequency
(which is proportional to Bo) and relative detection sensitivity. It is important
to note that the time needed to perform an MR measurement, either
spectroscopy or imaging, achieving a desired signal-to-noise (SIN) or quality
level, is proportional to the inverse square of the isotope sensitivity or the
spin (substance) concentration. Each factor of two improvement in SIN for
a given measurement requires a factor of 4 increase in measurement time.
On the other hand, for a given substance concentration the measurement
time required decreases approximately with the third power of Bo, so that
high-field in vitro studies have a considerable advantage over, low-field
clinical in vivo studies in terms of detection threshold. The abundant isotope
of carbon 12e has no nuclear spin; thus, the low sensitivity for 13e means
that labeling of substances is often necessary for biological applications.
1 Central Spectroscopy Department, German Cancer Research Center, 1m Neuenheimer
Feld 280, D-69120 Heidelberg, FRG
4 W.E. Hull
Table 1. Principal isotopes used for biological applications of MR
Isotope Natural Resonance frequency Detection Minimal concentrationb
abundance (%) at 11.7T (MHz) sensitivity· (nmol/g)
100 500 100 4
100 470 83 5
100 202 7 50
1.1 125 0.02 4000 (40")
• In relative units for equal molar concentrations of substance.
bMinimum metabolite detection threshold for a 30-min measurement at 1l.7T.
cFor >90% 13C labeling.
Since MR operates at radiofrequency energies rather than at optical, X-ray
or y-ray energies, it is a basically harmless but very insensitive technique
compared to other spectroscopic or radiological methods. However, this is
the price that we pay for the incomparably detailed molecular, biochemical,
and physiological information that MR can provide.
The exact resonance frequencies for a given isotope at various positions
in a molecule are sensitive to the local molecular structure. These effects,
called "chemical shifts," are proportional to Bo and are in the Hz to KHz
range. By convention, chemical shifts are usually expressed in units of ppm
relative to the resonance frequency of a chosen reference signal so that the
values are independent of Bo.
It is important to note that: (a) an MR spectrum is a fingerprint for
chemical structure, i.e., the position and form of the signals can be used to
identify molecular species; (b) mixtures can be analyzed without chromato
graphic separation; the area under a signal (its integral) is proportional to
the concentration of the substance; (c) signallinewidths contain information
about molecular mobility and chemical exchange rates; and (d) higher mag
netic fields improve signal separation (resolution) and detection sensitivity.
It is very important to realize that signal linewidths are roughly proportional
to molecular weight; macromolecules and tightly bound metabolites are not
normally detected or at best are seen as a very broad background signal. It is
of particular interest that the MR technique is truly nondestructive and can
be applied in a noninvasive manner in vivo.
There are a variety of ways to generate and manipulate MR signals to
provide: (a) purely chemical/structural information (spectroscopy); (b) purely
spatial information (imaging); and (c) both chemical and spatial information
(localized spectroscopy). The MR techniques used and their applications
(spectroscopy and imaging) are generally classified as in vitro or in vivo. In
vitro or "high-resolution" MR techniques are employed at field strengths of
Bo = 2-14 T to obtain detailed analytical information on:
- Homogeneous solutions or mixtures, cellular extracts
- Biofluids: urine, plasma, bile, CSF (typically 0.3-1.5 rnI)
Magnetic Resonance and Its Possible Applications in Nephrourology 5
- Solid tissue, biopsies (0.1-1 g)
- Cell suspensions (106_108 cells)
- Perfused cells in a bioreactor or gel matrix
- Perfused, functioning organ or cold preserved organ (e.g., up to 7T/21-
cm magnet for human kidneys)
In vivo MR methods are more or less noninvasive but involve some com
promises in sensitivity and resolution. Animal model studies can be per
=
formed at fields comparable to those for in vitro work, Bo 2-11.7T, while
clinical studies are limited to Bo = 1-4 T. The techniques of interest are:
- Implanted coils or special coils for externalized kidneys in animal models
(highest sensitivity)
- Surface coil techniques to study localized subcutaneous tumors, for
example, human renal cell carcinoma (RCC) xenografts on nude mice
- More general "whole-body" imaging and image-guided spectroscopic
techniques for internal organs (reduced sensitivity)
Some typical applications for the most important MR isotopes are the
following:
1H . Signals from a large number of molecules can be detected, i.e., metabolic
fingerprinting; high-resolution imaging and MR microscopy using the intense
signals from tissue water and fat; low-resolution imaging (0.1-10 cm3 voxels,
ranging from high-field animal studies to medium-field human studies) of
specific metabolites that occur in mM concentrations.
13 C. Only a few metabolites at high concentation are detectable in natural
abundance; labeled precursors can be used to trace metabolic pathways and
transport; two-dimensional IH/13C experiments can be used for metabolic
fingerprinting.
19p. High detection sensitivity; specific fluorine-containing analogs can
be used for studying metabolism or trapsport, for example, fluorosugars;
fluorine-containing antimetabolites, for example, fluoropyrimidines, are used
for chemotherapy; perftuorocompounds in blood substitutes can be used for
imaging with mm resolution.
31 P. For monitoring phosphate, phosphoester, and nucleotide levels to
determine intracellular pH and energy status for judging organ. viability,
studying phospholipid metabolism in tumors and monitoring therapy res
ponse; metabolic imaging requires ca. 1-100 cm3 voxels, depending on subject
and field strength. .