Small-Animal Molecular Imaging Methods

PET Clinics, 2008

Molecular imaging includes a range of techniques meant to visualize molecular events at the cellular level in living organisms in a noninvasive fashion. In the preclinical setting, the most interesting molecular imaging techniques are PET 1 and MR imaging with molecular contrast agents that allow in vivo accurate quantitation or semiquantitation of many molecular phenomena. Another important technique is CT with or without vascular or liver contrast agents. CT does not provide molecular information but is useful for observing the morphology of tissues and lesions (eg, to accurately measure a tumoral mass over time) because it is very fast and complements the data obtained by PET and MR imaging.

Journal of Cellular Biochemistry, 2002

X-ray micro-CT is currently used primarily to generate 3D images of micro-architecture (and the function that can be deduced from it) and the regional distribution of administered radiopaque indicators, within intact rodent organs or biopsies from large animals and humans. Current use of X-ray micro-CT can be extended in three ways to increase the quantitative imaging of molecular transport and accumulation within such specimens. (1) By use of heavy elements, other than the usual iodine, attached to molecules of interest or to surrogates for those molecules. The accumulation of the indicator in the physiological compartments, and the transport to and from such compartments, can be quantitated from the imaged spatial distribution of these contrast agents. (2) The high spatial resolution of conventional X-ray attenuation-based CT images can be used to improve the quantitative nature of radionuclide-based tomographic images (SPECT & PET) by providing correction for attenuation of the emitted gamma rays and the accurate delineation of physiological spaces known to selectively accumulate those indicators. Similarly, other imaging modalities which also localize functions in 2D images (such as histological sections subsequently obtained from the same specimen), can provide a synergistic combination with CT-based 3D microstructure. (3) By increasing the sensitivity and specificity of X-ray CT image contrast by use of methods such as: K-edge subtraction imaging, X-ray fluorescence imaging, imaging of the various types of scattered X-ray and the consequences of the change in the speed of X-rays through different tissues, such as refraction and phase shift. These other methods of X-ray imaging can increase contrast by more than an order of magnitude over that due to conventionally-used attenuation of X-ray. To fully exploit their potentials, much development of radiopaque indicators, scanner hardware and image reconstruction and analysis software will be needed.

Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2007

During the last decade we have observed a growing interest in in-vivo imaging techniques for small animals. This is due to the necessity of studying biochemical processes at a molecular level for pharmacology, genetic, and pathology investigations. Among the various ''molecular imaging'' techniques Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) have represented a valuable approach in such field. On the shadow of the successful application of combined PET-CT scanners in the clinical environment, multi-modality techniques have been recently transferred to small animal scanners. This paper reports on some recent advances in small animal PET, SPECT and CT scanners. An overview of the near future perspectives is also presented.

Einstein (São Paulo), 2016

Objective: To present the result of upgrading a clinical gamma-camera to be used to obtain in vivo tomographic images of small animal organs, and its application to register cardiac, renal and neurological images. Methods: An updated version of the miniSPECT upgrading device was built, which is composed of mechanical, electronic and software subsystems. The device was attached to a Discovery VH (General Electric Healthcare) gamma-camera, which was retired from the clinical service and installed at the Centro de Imagem Pré-Clínica of the Hospital Israelita Albert Einstein. The combined system was characterized, determining operational parameters, such as spatial resolution, magnification, maximum acceptable target size, number of projections, and acquisition and reconstruction times. Results: Images were obtained with 0.5mm spatial resolution, with acquisition and reconstruction times between 30 and 45 minutes, using iterative reconstruction with 10 to 20 iterations and 4 projection subsets. The system was validated acquiring in vivo tomographic images of the heart, kidneys and brain of normal animals (mice and adult rats), using the radiopharmaceuticals technetium-labeled hexakis-2-methoxy-isobutyl isonitrile (99m Tc-Sestamibi), technetiumlabeled dimercaptosuccinic acid (99m Tc-DMSA) and technetium-labeled hexamethyl propyleneamine oxime (99m Tc-HMPAO). Conclusion: This kind of application, which consists in the adaptation for an alternative objective of already existing instrumentation, resulted in a low-cost infrastructure option, allowing to carry out large scale in vivo studies with enhanced quality in several areas, such as neurology, nephrology, cardiology, among others.

Medical Physics, 2010

The use of small animal models in basic and preclinical sciences constitutes an integral part of testing new pharmaceutical agents prior to commercial translation to clinical practice. Whole-body small animal imaging is a particularly elegant and cost-effective experimental platform for the timely validation and commercialization of novel agents from the bench to the bedside. Biomedical imaging is now listed along with genomics, proteomics, and metabolomics as an integral part of biological and medical sciences. Miniaturized versions of clinical diagnostic modalities, including but not limited to microcomputed tomography, micromagnetic resonance tomography, microsinglephoton-emission tomography, micropositron-emission tomography, optical imaging, digital angiography, and ultrasound, have all greatly improved our investigative abilities to longitudinally study various experimental models of human disease in mice and rodents. After an exhaustive literature search, the authors present a concise and critical review of in vivo small animal imaging, focusing on currently available modalities as well as emerging imaging technologies on one side and molecularly targeted contrast agents on the other. Aforementioned scientific topics are analyzed in the context of cancer angiogenesis and innovative antiangiogenic strategies under-the-way to the clinic. Proposed hybrid approaches for diagnosis and targeted site-specific therapy are highlighted to offer an intriguing glimpse of the future.

Molecular Diagnosis & Therapy, 2014

Translational research is changing the practice of modern medicine and the way in which health problems are approached and solved. The use of small-animal models in basic and preclinical sciences is a major keystone for these kinds of research and development strategies, representing a bridge between discoveries at the molecular level and clinical implementation in diagnostics and/or therapeutics. The development of high-resolution in vivo imaging technologies provides a unique opportunity for studying disease in real time, in a quantitative way, at the molecular level, along with the ability to repeatedly and non-invasively monitor disease progression or response to treatment. The greatest advantages of preclinical imaging techniques include the reduction of biological variability and the opportunity to acquire, in continuity, an impressive amount of unique information (without interfering with the biological process under study) in distinct forms, repeated or modulated as needed, along with the substantial reduction in the number of animals required for a particular study, fully complying with 3R (Replacement, Reduction and Refinement) policies. The most suitable modalities for small-animal in vivo imaging applications are based on nuclear medicine techniques (essentially, positron emission tomography [PET] and single photon emission computed tomography [SPECT]), optical imaging (OI), computed tomography (CT), magnetic resonance imaging (MRI), magnetic resonance spectroscopy imaging (MRSI), and ultrasound. Each modality has intrinsic advantages and limitations. More recently, aiming to overcome the inherent limitations of each imaging modality, multimodality devices designed to provide complementary information upon the pathophysiological process under study have gained popularity. The combination of high-resolution modalities, like micro-CT or micro-MRI, with highly sensitive techniques providing functional information, such as micro-PET or micro-SPECT, will continue to broaden the horizons of research in such key areas as infection, oncology, cardiology, and neurology, contributing not only to the understanding of the underlying mechanisms of disease, but also providing efficient and unique tools for evaluating new chemical entities and candidate drugs. The added value of small-animal imaging techniques has driven their increasing use by pharmaceutical companies, contract research organizations, and research institutions.

Journal of Neural Transmission, 2005

Significant technological advancements required for imaging physiological function in small animals have been achieved in the last few years. Dedicated small animals PET scanners are now achieving resolutions that approach the one obtainable by autoradiographic methods, while still maintaining enough detection sensitivity to reliably measure biologically relevant parameters such as binding potentials or rate constants. Such developments have enabled researchers to explore in-vivo rodent models of human disease. The future in imaging now lies in the development of multi-modality imaging approaches, while the big challenge in the next few years will be for the chemists to develop tracers that are more specific and reflective of the functional condition under investigation, while miniaturizing the chemical synthesis related instrumentation.

The American Journal of Pathology, 2013

For the greater part of the last century, basic science research has been limited to in vitro studies of cellular processes and ex vivo tissue examination from suitable animal models of disease. In the last three decades, however, new techniques have been developed that permit the imaging of live animals using X-rays, radiotracer emissions, magnetic resonance signals, sound waves and optical fluorescence, and bioluminescence. The objective of this review is to provide a broad overview of common animal imaging modalities, with a focus on positron emission tomography (PET), single photon emission computed tomography (SPECT), and computed tomography (CT). Important examples, benefits, and limits of microPET/SPECT/CT technologies in current use, and their central role in improving our understanding of biological behavior and in facilitating the development of treatments from bench to bedside are included.

Cellular oncology : the official journal of the International Society for Cellular Oncology, 2006

Non-invasive real time in vivo molecular imaging in small animal models has become the essential bridge between in vitro data and their translation into clinical applications. The tremendous development and technological progress, such as tumour modelling, monitoring of tumour growth and detection of metastasis, has facilitated translational drug development. This has added to our knowledge on carcinogenesis. The modalities that are commonly used include Magnetic Resonance Imaging (MRI), Computed Tomography (CT), Positron Emission Tomography (PET), bioluminescence imaging, fluorescence imaging and multi-modality imaging systems. The ability to obtain multiple images longitudinally provides reliable information whilst reducing animal numbers. As yet there is no one modality that is ideal for all experimental studies. This review outlines the instrumentation available together with corresponding applications reported in the literature with particular emphasis on cancer research. Advan...

La radiologia medica, 2008

In these three words -genomics, proteomics and nanotechnologies -is the future of medicine of the third millennium, which will be characterised by more careful attention to disease prevention, diagnosis and treatment. Molecular imaging appears to satisfy this requirement. It is emerging as a new science that brings together molecular biology and in vivo imaging and represents the key for the application of personalized medicine. Micro-PET (positron emission tomography), micro-SPECT (single photon emission computed tomography), micro-CT (computed tomography), micro-MR (magnetic resonance), micro-US (ultrasound) and optical imaging are all molecular imaging techniques, several of which are applied only in preclinical settings on animal models. Others, however, are applied routinely in both clinical and preclinical setting. Research on small animals allows investigation of the genesis and development of diseases, as well as drug efficacy and the development of personalized therapies, through the study of biological processes that precede the expression of common symptoms of a pathology. Advances in molecular imaging were made possible only by collaboration among scientists in the fields of radiology, chemistry, molecular and cell biology, physics, mathematics, pharmacology, gene therapy and oncology. Although until now researchers have traditionally limited their interactions, it is only by increasing these connections that the current gaps in terminology, methods and approaches that inhibit scientific progress can be eliminated.