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Small Animal Imaging of Human Disease
The American Journal of Pathology, Vol. 182, No. 2, February 2013
ajp.amjpathol.org
Imaging Theme Issue
GUEST EDITORIAL Small Animal Imaging of Human Disease From Bench to Bedside and Back Linda A. Jelicks,*yz Herbert B. Tanowitz,x and Chris Albanese{k From the Departments of Physiology and Biophysics* and Pathology and Medicine,x the Gruss Magnetic Resonance Research Center,y and the M. Donald Blaufox microPET Imaging Center,z Albert Einstein College of Medicine of Yeshiva University, Bronx, New York; and the Departments of Oncology and Pathology{ and the Preclinical Imaging Research Laboratory,jj Georgetown University Medical Center, Washington, District of Columbia
Over the past decade, imaging devices for small animals have evolved from little more than boutique instruments, limited in many cases to the largest academic institutions, to extremely useful tools facilitating bench to bedside translational research at many colleges, universities, and pharmaceutical companies. It long has been known that a wealth of information can be garnered from noninvasive, longitudinal imaging studies performed in humans. However, the ability to perform similar studies in preclinical models, such as rodents, required a significant investment by both the equipment manufacturers and partnering academic laboratories to reverse engineer clinical imaging capabilities into small animaleenabled workstations. As a result of these partnerships, current imaging modalities are now applicable to small animals in the form of magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), bioluminescence imaging, ultrasound, and intravital imaging.
Noninvasive Imaging Studies Advances in using small animals as models that more faithfully recapitulate the human disease state in combination with technological advances in instrumentation hardware and software have positioned researchers in the field of small animal imaging to make unique contributions to medicine. Multimodality imaging and theranosticsdthe combination of diagnostics and therapeuticsdhave become increasingly important with advances in nanotechnology and molecular imaging. These combinations offer unique opportunities to study tissue metabolism and function as well as anatomy in small animal models of human disease. Copyright ª 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajpath.2012.11.015
In the early days there was a skepticism regarding the use of small animal imaging in models of human disease. This skepticism was underscored by the authors’ own personal experience when, in 1999, we submitted a manuscript describing the use of cardiac MRI to study the evolution of Chagas cardiomyopathy in the mouse model.1 One reviewer stated that it was unclear why we wanted to do these experiments and suggested that we simply infect mice and at various intervals sacrifice them and evaluate the pathology. The notion of serial, longitudinal, noninvasive studies on a single mouse over time was never considered by the reviewer. Interestingly, since that time many subsequent papers both by our group and, more importantly by others, have indeed used serial echocardiography, cardiac MRI, and microPET to evaluate cardiac structure and function in murine models of Chagas disease. In fact, many journals will not accept papers on small animal models of human heart diseases without these types of structural and functional studies. Perhaps predictably, PubMed is ever-growing in its inclusion of papers devoted to anatomical and functional imaging. A search of the term preclinical imaging returns 71 papers listed in 1999 to more 650 in 2011 (http://www. ncbi.nlm.nih.gov/pubmed, last accessed November 2012). Such experiments, combined with initiatives to follow drug delivery, develop contrast agents, and provide image-guided therapy in small animals, are now openly integrated with clinical applications. This reciprocal cross-fertilization between clinical and preclinical imaging promises to
Supported by NIH grants R01CA129003 (C.A.), ABC2 (C.A.) P30 CA51008 (Weiner, Director of the Lombardi Comprehensive Cancer Center, Georgetown University), and AI-076248 (H.B.T.). H.B.T. is Special Editor of the Imaging Theme Issue.
Guest Editorial Medical and technological advances + need
Clinical Imaging
Preclinical Imaging
Complex genetic and functional studies, novel applications/outcomes
Figure 1 Historically, clinical imaging has informed preclinical imaging and visa versa. This close association allows for the free exchange of ideas, approaches, and data, as well as complementation of clinical findings using animal models when necessary.
accelerate advances in novel imaging applications and quicken the development of new technologies and their uses (Figure 1).
The American Journal of Pathology
-
ajp.amjpathol.org
Imaging Theme Issue The reviews in this special Imaging Theme Issue of The American Journal of Pathology provide an overview of recent advances in small animal imaging and applications to studies of infectious diseases and cancer. These reviews are not meant to be an exhaustive treatment of the subject but rather a targeted introduction to afford those who are interested in a reference point to perform their own in-depth assessment of these modalities. Since preclinical MRI, PET, CT, SPECT, and ultrasound imaging have been extensively applied to animal models of cancer and infectious diseases, and bioluminescence has been shown to be a powerful technique for tracking tumorigenesis, bacteria, fungi, parasites, and viruses, we anticipate that more researchers and their institutions will recognize the value that noninvasive preclinical imaging provides, furthering its integration into basic and translational research.
Reference 1. Jelicks LA, Shirani J, Wittner M, Chandra M, Weiss LM, Factor SM, Bekirov I, Braunstein VL, Chan J, Huang H, Tanowitz HB: Application of cardiac gated magnetic resonance imaging in murine Chagas’ disease. Am J Trop Med Hyg 1999, 61:207e214
295
ajp.amjpathol.org
Imaging Theme Issue
GUEST EDITORIAL Small Animal Imaging of Human Disease From Bench to Bedside and Back Linda A. Jelicks,*yz Herbert B. Tanowitz,x and Chris Albanese{k From the Departments of Physiology and Biophysics* and Pathology and Medicine,x the Gruss Magnetic Resonance Research Center,y and the M. Donald Blaufox microPET Imaging Center,z Albert Einstein College of Medicine of Yeshiva University, Bronx, New York; and the Departments of Oncology and Pathology{ and the Preclinical Imaging Research Laboratory,jj Georgetown University Medical Center, Washington, District of Columbia
Over the past decade, imaging devices for small animals have evolved from little more than boutique instruments, limited in many cases to the largest academic institutions, to extremely useful tools facilitating bench to bedside translational research at many colleges, universities, and pharmaceutical companies. It long has been known that a wealth of information can be garnered from noninvasive, longitudinal imaging studies performed in humans. However, the ability to perform similar studies in preclinical models, such as rodents, required a significant investment by both the equipment manufacturers and partnering academic laboratories to reverse engineer clinical imaging capabilities into small animaleenabled workstations. As a result of these partnerships, current imaging modalities are now applicable to small animals in the form of magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), single photon emission computed tomography (SPECT), bioluminescence imaging, ultrasound, and intravital imaging.
Noninvasive Imaging Studies Advances in using small animals as models that more faithfully recapitulate the human disease state in combination with technological advances in instrumentation hardware and software have positioned researchers in the field of small animal imaging to make unique contributions to medicine. Multimodality imaging and theranosticsdthe combination of diagnostics and therapeuticsdhave become increasingly important with advances in nanotechnology and molecular imaging. These combinations offer unique opportunities to study tissue metabolism and function as well as anatomy in small animal models of human disease. Copyright ª 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajpath.2012.11.015
In the early days there was a skepticism regarding the use of small animal imaging in models of human disease. This skepticism was underscored by the authors’ own personal experience when, in 1999, we submitted a manuscript describing the use of cardiac MRI to study the evolution of Chagas cardiomyopathy in the mouse model.1 One reviewer stated that it was unclear why we wanted to do these experiments and suggested that we simply infect mice and at various intervals sacrifice them and evaluate the pathology. The notion of serial, longitudinal, noninvasive studies on a single mouse over time was never considered by the reviewer. Interestingly, since that time many subsequent papers both by our group and, more importantly by others, have indeed used serial echocardiography, cardiac MRI, and microPET to evaluate cardiac structure and function in murine models of Chagas disease. In fact, many journals will not accept papers on small animal models of human heart diseases without these types of structural and functional studies. Perhaps predictably, PubMed is ever-growing in its inclusion of papers devoted to anatomical and functional imaging. A search of the term preclinical imaging returns 71 papers listed in 1999 to more 650 in 2011 (http://www. ncbi.nlm.nih.gov/pubmed, last accessed November 2012). Such experiments, combined with initiatives to follow drug delivery, develop contrast agents, and provide image-guided therapy in small animals, are now openly integrated with clinical applications. This reciprocal cross-fertilization between clinical and preclinical imaging promises to
Supported by NIH grants R01CA129003 (C.A.), ABC2 (C.A.) P30 CA51008 (Weiner, Director of the Lombardi Comprehensive Cancer Center, Georgetown University), and AI-076248 (H.B.T.). H.B.T. is Special Editor of the Imaging Theme Issue.
Guest Editorial Medical and technological advances + need
Clinical Imaging
Preclinical Imaging
Complex genetic and functional studies, novel applications/outcomes
Figure 1 Historically, clinical imaging has informed preclinical imaging and visa versa. This close association allows for the free exchange of ideas, approaches, and data, as well as complementation of clinical findings using animal models when necessary.
accelerate advances in novel imaging applications and quicken the development of new technologies and their uses (Figure 1).
The American Journal of Pathology
-
ajp.amjpathol.org
Imaging Theme Issue The reviews in this special Imaging Theme Issue of The American Journal of Pathology provide an overview of recent advances in small animal imaging and applications to studies of infectious diseases and cancer. These reviews are not meant to be an exhaustive treatment of the subject but rather a targeted introduction to afford those who are interested in a reference point to perform their own in-depth assessment of these modalities. Since preclinical MRI, PET, CT, SPECT, and ultrasound imaging have been extensively applied to animal models of cancer and infectious diseases, and bioluminescence has been shown to be a powerful technique for tracking tumorigenesis, bacteria, fungi, parasites, and viruses, we anticipate that more researchers and their institutions will recognize the value that noninvasive preclinical imaging provides, furthering its integration into basic and translational research.
Reference 1. Jelicks LA, Shirani J, Wittner M, Chandra M, Weiss LM, Factor SM, Bekirov I, Braunstein VL, Chan J, Huang H, Tanowitz HB: Application of cardiac gated magnetic resonance imaging in murine Chagas’ disease. Am J Trop Med Hyg 1999, 61:207e214
295