Small Animal Imaging: Basics and Practical Guide

871 Pages·2017·47.6 MB·English

by  Fabian Kiessling, Bernd J. Pichler, Peter Hauff (eds.)

Fabian Kiessling
Bernd J. Pichler
Peter Hauff
Editors
Small Animal Imaging
Basics and Practical Guide
Second Edition
123
Small Animal Imaging
Fabian Kiessling • Bernd J. Pichler
Peter Hauff
Editors
Small Animal Imaging
Basics and Practical Guide
Second Edition
Editors
Fabian Kiessling Peter Hauff
Universitätsklinikum Aachen Bayer AG, Drug Discovery
Aachen Pharmaceuticals
Germany Berlin
Germany
Bernd J. Pichler
Universitätsklinikum Tübingen
Tübingen
Germany
ISBN 978-3-319-42200-8 ISBN 978-3-319-42202-2 (eBook)
DOI 10.1007/978-3-319-42202-2
Library of Congress Control Number: 2016959560
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Preface to the Second Edition
This textbook is a practical guide to the use of small animal imaging in
preclinical research that will assist in the choice of imaging modality and
contrast agent and in study design, experimental setup, and data evaluation.
All established imaging modalities are discussed in detail, with the assistance
of numerous informative illustrations, and the new edition also includes an
extended introduction to emerging technologies such as photoacoustic imag-
ing, hyperpolarized imaging, and novel intravital microscopy techniques.
The second edition includes a variety of other novel features: The section
on “Special Applications” has been expanded to include chapters on meta-
bolic imaging, cell tracking, transplant labeling, and imaging of infectious
diseases. Additional useful hints are provided on the installation of a small
animal unit, study planning, animal handling, and the cost-effective perfor-
mance of small animal imaging. Furthermore, since many small animal imag-
ing studies fail owing to inadequate contrast agents, a chapter has been added
discussing concepts and materials for diagnostic probes in the context of
pharmacokinetic demands. Finally, cross-calibration methods and data post-
processing are also considered in depth.
While the second edition of this textbook has been updated to encompass
emerging new imaging modalities, methods, and applications, the focus
remains on practical basics. It will be an invaluable aid for researchers, stu-
dents, and technicians involved in research into and applications of small
animal imaging.
Aachen, Germany Fabian Kiessling
Tuebingen, Germany Bernd J. Pichler
Berlin, Germany Peter Hauff
v
Preface to the First Edition
During the last decade there have been tremendous advances in molecular
biology and many important regulatory pathways of diseases have been iden-
tified. Along with these, genomics and proteomics are currently being imple-
mented as important tools in the clinical workflow. On the other hand, there
has been significant progress in non-invasive imaging technologies. Nowadays
it is possible to scan an entire patient by CT and MRI with high spatial resolu-
tion and with exquisite tissue contrast within seconds or minutes. Contrast
agents can be applied and their accumulation monitored dynamically to gain
functional data about tissue vascularisation, perfusion and permeability.
In addition, imaging modalities that are highly sensitive to administered
radiolabelled probes like PET and SPECT enable us to elucidate changes in
metabolism and proliferation as well as in molecular profiles of tissues with
high sensitivity.
Besides these clinically established methods there are novel promising
imaging tools and applications which are currently in the stage of develop-
ment. These include, for example, molecular ultrasound, high field MRI as
well as photoacoustic and optical imaging.
Beyond this, imaging modalities have been developed further to such a
high degree that they are now able to be applied to very small animals like
mice and rats for diagnostic purposes. Current dedicated small animal imag-
ing modalities allow the in vivo assessment of morphological structures or
functional, metabolic and molecular processes in mice and rats as in humans.
Utilizing these tools in the preclinical arena can also significantly improve
the identification and development of novel diagnostic or therapeutic drugs
and facilitate the translation of preclinical findings to the clinics and vice
versa. Important surrogate markers and imaging strategies can be developed
and tested along with novel therapeutic drugs. Longitudinal data can be
obtained from the same animal, which means that the animal can serve as its
own control. In this manner the disease progression or the pharmacological
effect of a drug can be monitored much more effectively. As a result high
statistical power can be achieved with a reduced number of animals, which
lowers costs and recognizes ethical considerations on animal protection.
Non-invasive imaging also has the potential to identify therapeutic drugs
with limited effectiveness at a very early stage of its development. Therefore
it can be used as a preclinical screening tool to boost the clinical drug success
rate of currently one in five to, for example, one in three which would signifi-
cantly lower the development cost for a new drug.
vii
viii Preface to the First Edition
Nevertheless, although there is no doubt about the potentially beneficial
role of small animal imaging in preclinical research it has not been broadly
established. Many imaging applications have never exceeded the Proof of
Principle status and are so time consuming that it is not realistic to use them
in preclinical research routinely. This often goes in line with limited data
reproducibility. Besides this, in many publications non-invasive imaging acts
as an appealing embellishment without having evident impact on its scientific
gist. These current obstacles for the implementation of non-invasive small
animal imaging are aggravated by failing studies where either a suboptimal
imaging modality or contrast was chosen or where failures were made in
statistical study planning and animal handling.
Thus, this book aims to be a guide for all who intend to implement small
animal imaging in their routine research. It provides concrete hints on how an
effective small animal unit can be built up, how the personnel should be
trained, where pitfalls in study planning are and which imaging modalities
should be used for different purposes. Also, basic problems like the choice of
the correct anesthesia and its influence on animal physiology as well as tech-
niques of catheterization for drug administration are considered. Finally this
book specifically serves as a guide for the correct and comprehensive quanti-
fication and interpretation of imaging data.
We very much hope that this book will be of significant value for our read-
ers in their daily work and we wish every success in the exciting and creative
field of preclinical imaging.
Aachen, Germany Fabian Kiessling
Tuebingen, Germany Bernd J. Pichler
Berlin, Germany Peter Hauff
Contents
Part I Role of Small Animal Imaging
1 Noninvasive Imaging for Supporting Basic Research . . . . . . . . . . 3
Pat Zanzonico
2 Non-invasive Imaging in the Pharmaceutical Industry . . . . . . . . 33
Sally-Ann Emmas, Paul D. Hockings, and John C. Waterton
3 Designing a Small Animal Imaging Center . . . . . . . . . . . . . . . . . 47
David Stout
4 Noninvasive Small Rodent Imaging: Significance
for the 3R Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 69
Nicolau Beckmann and Birgit Ledermann
Part II Study Planning and Animal Preparation
5 Institutional Preconditions for Small Animal Imaging . . . . . . . . 91
René H. Tolba
6 Statistical Considerations for Animal Imaging Studies. . . . . . . 101
Hannes-Friedrich Ulbrich
7 Anesthesia and Analgesia in Laboratory Animals . . . . . . . . . . . 117
Marc Hein, Anna B. Roehl, and René H. Tolba
8 Drug Administration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127
Peter Hauff and Klaus Nebendahl
Part III Imaging Modalities and Probes
9 How to Choose the Right Imaging Modality . . . . . . . . . . . . . . . 155
Fabian Kiessling, Bernd Pichler, and Peter Hauff
10 How to Identify Suitable Molecular Imaging Biomarkers . . . . 163
Norman Koglin, Andre Mueller, Andrew W. Stephens,
and Ludger M. Dinkelborg
11 Concepts in Diagnostic Probe Design . . . . . . . . . . . . . . . . . . . . . 177
Igor Jacobs, Gustav J. Strijkers, Henk M. Keizer,
Henk M. Janssen, Hisataka Kobayashi, and Klaas Nicolay
ix
x Contents
12 X-Ray and X-Ray-CT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
Robert Brauweiler, Klaus Engelke, Martin Hupfer,
Willi A. Kalender, Marek Karolczak, and Hubertus Pietsch
13 MRI . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Aileen Schroeter, Markus Rudin, Eliana Gianolio,
Alessandra Viale, Daniela Delli Castelli, Silvio Aime,
Jan-Bernd Hövener, Jessica A.M. Bastiaansen,
Arnaud Comment, Stephan Düwel,
Jan H. Ardenkjaer-Larsen, and Markus Becker
14 Ultrasound . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 325
Stuart Foster, J.M. Hyvelin, Minalini Lakshman,
Andrew Needles, I. Tardy, and François Tranquart
15 PET and SPECT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Clemens Decristoforo, Uwe Haberkorn, Roland Haubner,
Walter Mier, and Sibylle I. Ziegler
16 Optical Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 403
Frauke Alves, Julia Bode, Peter Cimalla, Ingrid Hilger,
Martin Hofmann, Volker Jaedicke, Edmund Koch,
Kai Licha, Timo Rademakers, Daniel Razansky,
and Marc A.M.J. van Zandvoort
17 Multimodal Imaging and Image Fusion . . . . . . . . . . . . . . . . . . . 491
Hans F. Wehrl, Mario Amend, and André Thielcke
Part IV Ex Vivo Validation Methods
18 In Vitro Methods for In Vivo Quantitation of PET
and SPECT Imaging Probes: Autoradiography
and Gamma Counting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511
David Stout and Cinthia Pastuskovas
Part V Data Postprocessing
19 Qualitative and Quantitative Data Analysis . . . . . . . . . . . . . . . . 529
Felix Gremse
20 Guidelines for Nuclear Image Analysis . . . . . . . . . . . . . . . . . . . . 547
Martin S. Judenhofer, Stefan Wiehr, Damaris Kukuk,
Kristina Fischer, and Bernd J. Pichler
21 Kinetic Modeling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
J. van den Hoff
22 Data Management in Small Animal Imaging:
Conceptual and Technical Considerations . . . . . . . . . . . . . . . . . 581
J. Maus and F. Hofheinz
Contents xi
Part VI Special Applications
23 Cell Tracking and Transplant Imaging . . . . . . . . . . . . . . . . . . . . 593
Laura C. Rose and Jeff W. M. Bulte
24 Beta Cell Imaging as Part of
“Imaging on Metabolic Diseases” . . . . . . . . . . . . . . . . . . . . . . . . 605
M. Brom, W.A. Eter, I. van der Kroon, S.M.A. Willekens,
A. Eek, M. Boss, M. Buitinga, and M. Gotthardt
25 In Vivo Preclinical Imaging of Developmental Biology . . . . . . . 627
Katrien Vandoorne, Tal Raz, Stav Sapoznik, Inbal E. Biton,
Joel R. Garbow, and Michal Neeman
26 Imaging in Gynecology Research . . . . . . . . . . . . . . . . . . . . . . . . 651
Matthias W. Laschke and Michael D. Menger
27 Imaging in Cardiovascular Research . . . . . . . . . . . . . . . . . . . . . 663
Michael Schäfers, Michael Kuhlmann, Lars Stegger,
Klaus Schäfers, and Sven Hermann
28 Imaging in Neurooncology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 689
Yannic Waerzeggers, Bastian Zinnhardt,
Alexandra Winkeler, Parisa Monfared, Sonja Schelhaas,
Thomas Viel, and Andreas H. Jacobs
29 Imaging in Neurology Research II: Exploring
Plasticity and Cognitive Networks by In Vivo MRI . . . . . . . . . . 727
J. Hamaide, L. Van Ruijssevelt, F. Kara, G. De Groof,
and A. Van der Linden
30 Imaging in Neurology Research III: Neurodegenerative
Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761
Heike Endepols and Bernd Neumaier
31 When Photons Meet Protons: Optogenetics,
Calcium Signal Detection, and fMRI in Small Animals . . . . . . 773
Xin Yu
32 Imaging in Oncology Research . . . . . . . . . . . . . . . . . . . . . . . . . . 793
Wolfgang A. Weber and Fabian Kiessling
33 PET Imaging in Immunology . . . . . . . . . . . . . . . . . . . . . . . . . . . 821
Melissa N. McCracken and Owen N. Witte
34 Molecular Imaging of Infectious Diseases . . . . . . . . . . . . . . . . . 845
Anna-Maria Rolle and Stefan Wiehr
Appendix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 857
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 863