Small Animal Imaging: Basics and Practical Guide PDF
Preview Small Animal Imaging: Basics and Practical Guide
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 © Springer International Publishing AG 2017 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, 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. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland 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
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