A new preclinical ultrasound platform for widefield 3D imaging of rodents
Tomasz J. CzernuszewiczVirginie PapadopoulouJuan D. RojasRajalekha RajamahendiranJonathan PerdomoJames ButlerMax HarlacherGraeme O’ConnellDženan ZukićStephen AylwardPaul A. DaytonRyan C. Gessner
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Noninvasive in vivo imaging technologies enable researchers and clinicians to detect the presence of disease and longitudinally study its progression. By revealing anatomical, functional, or molecular changes, imaging tools can provide a near real-time assessment of important biological events. At the preclinical research level, imaging plays an important role by allowing disease mechanisms and potential therapies to be evaluated noninvasively. Because functional and molecular changes often precede gross anatomical changes, there has been a significant amount of research exploring the ability of different imaging modalities to track these aspects of various diseases. Herein, we present a novel robotic preclinical contrast-enhanced ultrasound system and demonstrate its use in evaluating tumors in a rodent model. By leveraging recent advances in ultrasound, this system favorably compares with other modalities, as it can perform anatomical, functional, and molecular imaging and is cost-effective, portable, and high throughput, without using ionizing radiation. Furthermore, this system circumvents many of the limitations of conventional preclinical ultrasound systems, including a limited field-of-view, low throughput, and large user variability.Keywords:
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Other SectionsABSTRACTINTRODUCTIONIN VIVO MOLECULAR IMAGINGIN VIVO SINGLE CELL IMAGINGACKNOWLEDGEMENTSCONFLICTS OF INTERESTFIGURESTABLEREFERENCES
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In vivo molecular imaging is a powerful tool to analyze the human body. Precision medicine is receiving high attention these days, and molecular imaging plays an important role as companion diagnostics in precision medicine. Nuclear imaging with PET or SPECT and optical imaging technologies are used for in vivo molecular imaging. Nuclear imaging is superior for quantitative imaging, and whole-body analysis is possible even for humans. Optical imaging is superior due to its ease of use, and highly targeted specific imaging is possible with activatable agents. However, with optical imaging using fluorescence, it is difficult to obtain a signal from deep tissue and quantitation is difficult due to the attenuation and scattering of the fluorescent signal. Recently, to overcome these issues, optoacoustic imaging has been used in in vivo imaging. In this article, we review in vivo molecular imaging with nuclear and optical imaging and discuss their utility for precision medicine.
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Translational research aims to provide direct support for advancing novel treatment approaches in oncology towards improving patient outcomes. Preclinical studies have a central role in this process and the ability to accurately model biological and physical aspects of the clinical scenario in radiation oncology is critical to translational success. The use of small animal irradiators with disease relevant mouse models and advanced in vivo imaging approaches offers unique possibilities to interrogate the radiotherapy response of tumors and normal tissues with high potential to translate to improvements in clinical outcomes. The present review highlights the current technology and applications of small animal irradiators, and explores how these can be combined with molecular and functional imaging in advanced preclinical radiotherapy research.
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Abstract For years, low reproducibility of preclinical trials and poor translation of promising preclinical therapies to the clinic have posed major challenges to translational research in most biomedical fields. To overcome the limitations that stand between experimental and clinical research, international consortia have attempted to establish standardized guidelines for study design and for reporting the resulting data. In addition, multicenter preclinical randomized controlled trials (p RCT s) have been proposed as a suitable tool for ‘bridging the gap’ between experimental research and clinical trials. We recently reported the design and results of the first such p RCT in which we confirmed the feasibility of using a coordinated approach with standardized protocols in collaboration with independent multinational research centers. However, despite its successes, this first p RCT also had several difficulties, particularly with respect to following the protocols established in the study design and analyzing the data. Here, we review our experiences performing the study, and we analyze and discuss the lessons learned from performing the first p RCT . Moreover, we provide suggestions regarding how obstacles can be overcome to improve the performance and outcome of future p RCT studies. image Translational research is hampered by low reproducibility of preclinical studies and countless failed clinical trials. International consortia have proposed preclinical multicenter trials as an intermediate step to overcome this ‘translational roadblock’. We have recently performed the first such preclinical randomized controlled trial (pRCT) by adopting key elements of clinical study design to preclinical research. In this review, we discuss the lessons learned from this trial and provide suggestions how to optimize future pRCTs. This article is part of the 60th Anniversary special issue .
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Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo . In most molecular imaging approaches, probes are used to bind to disease‐specific biomarkers highlighting disease target sites. In recent years, a new subset of molecular imaging probes, known as bioresponsive molecular probes, has been developed. These probes generally benefit from signal enhancement at the site of interaction with its target. There are mainly two classes of bioresponsive imaging probes. The first class consists of probes that show direct activation of the imaging label (from “off” to “on” state) and have been applied in optical imaging and magnetic resonance imaging (MRI). The other class consists of probes that show specific retention of the imaging label at the site of target interaction and these probes have found application in all different imaging modalities, including photoacoustic imaging and nuclear imaging. In this review, we present a comprehensive overview of bioresponsive imaging probes in order to discuss the various molecular imaging strategies. The focus of the present article is the rationale behind the design of bioresponsive molecular imaging probes and their potential in vivo application for the detection of endogenous molecular targets in pathologies such as cancer and cardiovascular disease. Copyright © 2015 John Wiley & Sons, Ltd.
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After completing this article, readers should be able to:
1. Describe the emerging field of in vivo molecular imaging.
2. List the various imaging modalities that have been used to detect molecules and track cells in vivo and discuss the basic molecular strategies and principles.
3. Describe several of the selective events, such as binding, enzymatic activation, or molecular switches, that make in vivo imaging of cells and molecules possible.
4. Delineate the strengths and weakness of current imaging strategies.
5. List combined imaging modalities and their use in molecular imaging.
Following cells and molecules in vivo has been a fundamental difficulty in biomedical research. The technologies in the field of in vivo molecular imaging are aimed at obtaining spatiotemporal information about in vivo processes as they occur; that is, monitoring cellular and molecular changes in response to a variety of stimuli in intact animals and eventually in humans. Understanding basic biologic and biochemical mechanisms is required to develop the tools that will enable access to this information.
Traditional imaging modalities largely depend on physical parameters, such as absorption in ultrasonography, x-ray attenuation, or optical scattering, which reveal primarily structural information. For molecular imaging, unique signatures are generated using molecular biology methods that distinctly label host cells, microbial pathogens, tumor cells, or transplanted tissues. These can be detected in vivo by conventional and novel imaging modalities and can be used to examine molecular mechanisms of pathogenesis, facilitate earlier disease detection, and permit evaluation of therapeutic outcomes. The molecular targets for imaging may include DNA, RNA, protein, or protein function. Imaging of inherent levels of DNA, RNA, and protein is difficult, but protein function can be exploited readily for imaging and can be used in reporter gene approaches to create surrogate markers for processes such as messenger RNA (mRNA) and protein synthesis.1,2, …
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Advancements in medical imaging have brought about unprecedented changes in the in vivo assessment of cancer. Positron emission tomography, single photon emission computed tomography, optical imaging, and magnetic resonance imaging are the primary tools being developed for oncologic imaging. These techniques may still be in their infancy, as recently developed chemical molecular probes for each modality have improved in vivo characterization of physiologic and molecular characteristics. Herein, we discuss advances in these imaging techniques, and focus on the major design strategies with which molecular probes are being developed.
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