Department of Radiology, Harvard University HMS/MGH, Charlestown, USA
U2R2M, CNRS and Université Paris–Sud, Orsay, France
Unité d′Imagerie de l′Expression des Gènes, INSERM, Orsay, Franc
This book describes the new imaging techniques being developed to monitor physiological, cellular and subcellular function within living animals. This exciting field of imaging science brings together physics, chemistry, engineering, biology and medicine to yield powerful and versatile imaging approaches. By combining advanced non–invasive imaging technologies with new mechanisms for visualizing biochemical events and protein and gene function, non–invasive vertebrate imaging enables the in vivo study of biology and offers rapid routes from basic discovery to drug development and clinical application. Combined with the availability of an increasing number of animal models of human disease, and the ability to perform longitudinal studies of disease evolution and of the long–term effects of therapeutic procedures, this new technology offers the next generation of tools for biomedical research.
Well illustrated, largely in colour, the book reviews the most common and technologically advanced methods for vertebrate imaging, presented in a clear, comprehensive format. The basic principles are described, followed by several examples of the use of imaging in the study of living multicellular organisms, concentrating on small animal models of human diseases. The book illustrates:
- The types of information that can be obtained with modern in vivo imaging;
- The substitution of imaging methods for more destructive histological techniques;
- The advantages conferred by in vivo imaging in building a more accurate picture of the response of tissues to stimuli over time while significantly reducing the number of animals required for such studies.
Part 1 describes current techniques in in vivo imaging, providing specialists and laboratory scientists from all disciplines with clear and helpful information regarding the tools available for their specific research field. Part 2 looks in more detail at imaging organ development and function, covering the brain, heart, lung and others. Part 3 describes the use of imaging to monitor various new types of therapy, following the reaction in an individual organism over time, e.g. after gene or cell therapy.
Most chapters are written by teams of physicists and biologists, giving a balanced coherent description of each technique and its potential applications.
The book is aimed at a broad audience conducting research in areas such as biochemistry, physiology, developmental biology, oncology and pharmacology. While written primarily for those already engaged in imaging studies, it will also be of interest to scientists from other disciplines looking for an entry point into the field of in vivo imaging in small animals.
1 Nuclear Magnetic Resonance Imaging and Spectroscopy (Anne Leroy–Willig and Danielle Geldwerth–Feniger).
1.1 Magnets and magnetic field.
1.2 Nuclear magnetization.
1.3 Excitation and return to equilibrium of nuclear magnetization.
1.4 The NMR hardware: RF coils and gradient coils (more technology).
1.5 NMR spectroscopy: the chemical encoding.
1.6 How to build NMR images: the spatial encoding.
1.7 MRI and contrast.
1.8 Sensitivity, spatial resolution and temporal resolution.
1.9 Contrast agents for MRI.
1.10 Imaging of other nuclei.
1.11 More parameters contributing to MRI contrast.
1.12 More about applications.
2 High Resolution X–ray Microtomography: Applications in Biomedical Research (Nora De Clerck and Andrei Postnov).
2.1 Principles of tomography.
2.3 Contribution of microtomography to biomedical imaging.
3 Ultrasound Imaging (S. Lori Bridal, Jean–Michel Correas and Genevieve Berger).
3.1 Principles of ultrasonic imaging and its adaptation to small laboratory animals.
3.2 Pulse–echo transmission.
3.3 Ultrasonic transducers.
3.4 From echoes to images.
3.5 Blood flow and tissue motion.
3.6 Non–linear and contrast imaging.
4 In Vivo Radiotracer Imaging (Bertrand Tavitian, Regine Trebossen, Roberto Pasqualini and Frederic Dolle´).
4.2 Interaction of gamma rays with matter.
4.3 Radiotracer imaging with gamma emitters.
4.4 Detection of positron emitters.
4.5 Image properties and analysis.
4.6 Radiochemistry of gamma–emitting radiotracers.
4.7 Radiochemistry of positron–emitting radiotracers.
4.8 Major radiotracers and imaging applications.
5 Optical Imaging and Tomography (Antoine Soubret and Vasilis Ntziachristos).
5.1 Light tissue interactions.
5.2 Light propagation in tissues.
5.3 Reconstruction and inverse problem.
5.4 Fluorescence molecular tomography (FMT).
6 Optical Microscopy in Small Animal Research (Rakesh K. Jain, Dai Fukumura, Lance Munn and Edward Brown).
6.1 Confocal laser scanning microscopy.
6.2 Multiphoton laser scanning microscopy.
6.3 Variants for In vivo imaging.
6.4 Surgical preparations.
7 New Radiotracers, Reporter Probes and Contrast Agents (Coordinated by Bertrand Tavitian).
7.0 Introduction (Bertrand Tavitian).
7.1 New radiotracers (Bertrand Tavitian, Roberto Pasqualini and Frederic Dolle´).
7.2 Multimodal constructs for magnetic resonance imaging (Willem J.M. Mulder, Gustav J. Strijkers and Klaas Nicolay).
7.3 Fluorescence reporters for biomedical imaging (Benedict Law and Ching–Hsuan Tung).
7.4 New contrast agents for NMR (Silvio Aime).
7.5 Imaging techniques reporter gene imaging agents (Huongfeng Li and Andreas H. Jacobs).
8 Multi–Modality Imaging (Coordinated by Vasilis Ntziachristos).
8.0 Introduction (Vasilis Ntziachristos).
8.1 Concurrent imaging versus computer–assisted registration (Fred S. Azar).
8.2 Combination of SPECT and CT (Jan Grimm).
8.3 FMT registration with MRI (Vasilis Ntziachristos).
9 Brain Imaging (Coordinated by Anne Leroy–Willig).
9.0 Introduction (Anne Leroy–Willig).
9.1 Bringing amyloid into focus with MRI microscopy (Greet Vanhoutte and Annemie Van der Linden).
9.2 Cerebral blood volume and BOLD contrast MRI unravels brain responses to ambient temperature fluctuations in fish (Annemie Van der Linden).
9.3 Assessment of functional and neuroanatomical re–organization after experimental stroke using MRI (Jet P. van der Zijden and Rick M. Dijkhuizen).
9.4 Brain activation and blood flow studies with speckle imaging (Andrew K. Dunn).
9.5 Manganese–enhanced MRI of the songbird brain: a dynamic window on rewiring brain circuits encoding a versatile behaviour (Vincent Van Meir and Annemie Van der Linden).
9.6 Functional MRI in awake behaving monkeys (Wim Vanduffel, Koen Nelissen, Denis Fize and Guy A. Orban).
9.7 Multimodal evaluation of mitochondrial impairment in a primate model of Huntington s disease (Vincent Lebon and Philippe Hantraye).
10 Imaging of Heart, Muscle, Vessels (Coordinated by Yves Fromes).
10.0 Introduction (Yves Fromes).
10.1 Cardiac structure and function (Yves Fromes).
10.2 Evaluation of therapeutic approaches in muscular dystrophy using MRI (Valerie Allamand).
10.3 Canine muscle oxygen saturation: evaluation and treatment of M–type phosphofructokinase deficiency (Kevin McCully and Urs Giger).
10.4 In vivo assessment of myocardial perfusion by NMR technology (Jorg. U.G. Streif, Matthias Nahrendorf and Wolfgang R. Bauer).
10.5 Ultrasound microimaging of strain in the mouse heart (F. Stuart Foster).
10.6 MR imaging of experimental atherosclerosis (Willem J.M. Mulder, Gustav J. Strijkers, Zahi A. Fayad and Klaas Nicolay).
11 Tumor Imaging (Coordinated by Vasilis Ntziachristos).
11.0 Introduction (Vasilis Ntziachristos).
11.1 Dynamic contrast–enhanced MRI of tumour angiogenesis (Charles Andre´ Cuenod, Laure Fournier, Daniel Balvay, Clement Pradel, Nathalie Siauve and Olivier Clement).
11.2 Liver tumours: Evaluation by functional computed tomography (Charles Andre Cuenod, Laure Fournier, Nathalie Siauve and Olivier Clement).
11.3 Early detection of grafted Wilms tumours (Erwan Jouannot).
11.4 Angiogenesis study using ultrasound imaging (Olivier Lucidarme).
11.5 Nuclear imaging of apoptosis in animal tumour models (Silvana Del Vecchio and Marco Salvatore).
11.6 Optical imaging of tumour–associated protease activity (Benedict Law and Ching–Hsuan Tung).
11.7 Tumour angiogenesis and blood flow (Rakesh K. Jain, Dai Fukumura, Lance L. Munn and Edward B. Brown).
11.8 Optical imaging of apoptosis in small animals (Eyk Schellenberger).
11.9 Fluorescence molecular tomography (FMT) of angiogenesis (Xavier Montet, Vasilis Ntziachristos, and Ralph Weissleder).
11.10 High resolution X–ray microtomography as a tool for imaging lung tumours in living mice (Nora De Clerck and Andrei Postnov).
12 Other Organs (Coordinated by Anne Leroy–Willig).
12.0 Introduction (Anne Leroy–Willig).
12.1 3D imaging of embryos and mouse organs by Optical Projection Tomography (James Sharpe).
12.2 Visualizing early Xenopus development with time lapse microscopic MRI (Cyrus Papan and Russell E. Jacobs).
12.3 Ultrasonic quantification of red blood cells development in mice (Johann Le Floch).
12.4 Placental perfusion MR imaging with contrast agent in a mouse model (Nathalie Siauve, Laurent Salomon and Charles Andre Cuenod).
12.5 Characterization of nephropathies and monitoring of renal stem cell therapies (Nicolas Grenier, Olivier Hauger, Yahsou Delmas and Christian Combe).
12.6 Optical imaging of lung inflammation (Jodi Haller).
12.7 Optical imaging in rheumatoid arthritis (Andreas Wunder).
13 Gene Therapy (Markus Klein and Andreas H. Jacobs).
13.1 Expression systems for genes of interest (GOI).
13.2 Gene delivery systems (vectors).
13.3 Suicide gene therapy.
13.4 Non–suicide gene therapy.
13.5 Imaging of gene expression.
13.6 Diseases targeted by gene therapy.
14 Cellular Therapies and Cell Tracking (Coordinated by Yves Fromes).
14.0 Introduction (Yves Fromes).
14.1 Are stem cells attracted by pathology? The case for cellular tracking by serial in vivo MRI (Michel Modo).
14.2 Cell tracking using MRI (V t Herynek).
14.3 Cell labelling strategies for in vivo molecular MR imaging (Mathias Hoehn).
14.4 Animal imaging and medical challenges – cell labelling and molecular imaging (Yannic Waerzeggers, and Andreas H. Jacobs).
Anne Leroy–Willig. Université Paris–Sud, France
Bertrand Tavitian. Unité d′Imagerie de l′Expression des Genes, CEA – SHFJ – INSERM ERITM, Orsay Cedex, France