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Davison C.A.,University of Notre Dame | Chapman S.E.,Notre Dame Integrated Imaging Facility | Sasser T.A.,University of Notre Dame | Sasser T.A.,Carestream | And 4 more authors.
Current Molecular Medicine | Year: 2013

Tumor heterogeneity is recognized as a major issue within clinical oncology, and the concept of personalized molecular medicine is emerging as a means to mitigate this problem. Given the vast number of cancer types and subtypes, robust pre-clinical models of cancer must be studied to interrogate the molecular mechanisms involved in each scenario. In particular, mouse models of tumor metastasis are of critical importance for pre-clinical cancer research at the cancer cell molecular level. In many of these experimental systems, tumor cells are injected intravenously, and the distribution and proliferation of these cells are subsequently analyzed via ex vivo methods. These techniques require large numbers of animals coupled with time-consuming histological preparation and analysis. Herein, we demonstrate the use of two facile and noninvasive imaging techniques to enhance the study of a pre-clinical model of breast cancer metastasis in the lung. Breast cancer cells were labeled with a near-infrared fluorophore that enables their visualization. Upon injection into a living mouse, the distribution of the cells in the body was detected and measured using whole animal fluorescence imaging. X-ray computed tomography (CT) was subsequently used to provide a quantitative measure of longitudinal tumor cell accumulation in the lungs over six weeks. A nuclear probe for lung perfusion, 99mTc-MAA, was also imaged and tested during the time course using single photon emission computed tomography (SPECT). Our results demonstrate that optical fluorescence methods are useful to visualize cancer cell distribution patterns that occur immediately after injection. Longitudinal imaging with X-ray CT provides a convenient and quantitative avenue to measure tumor growth within the lung space over several weeks. Results with nuclear imaging did not show a correlation between lung perfusion (SPECT) and segmented lung volume (CT). Nevertheless, the combination of animal models and noninvasive optical and CT imaging methods provides better research tools to study cancer cell differences at the molecular level. Ultimately, the knowledge gleaned from these improved studies will aid researchers in uncovering the mechanisms mediating breast cancer metastasis, and eventually improve the treatments of patients in the clinic. © 2013 Bentham Science Publishers.

Wathen C.A.,University of Notre Dame | Foje N.,University of Notre Dame | van Avermaete T.,University of Notre Dame | Miramontes B.,University of Notre Dame | And 7 more authors.
Sensors (Switzerland) | Year: 2013

X-ray Computed Tomography (CT) is one of the most commonly utilized anatomical imaging modalities for both research and clinical purposes. CT combines high-resolution, three-dimensional data with relatively fast acquisition to provide a solid platform for non-invasive human or specimen imaging. The primary limitation of CT is its inability to distinguish many soft tissues based on native contrast. While bone has high contrast within a CT image due to its material density from calcium phosphate, soft tissue is less dense and many are homogenous in density. This presents a challenge in distinguishing one type of soft tissue from another. A couple exceptions include the lungs as well as fat, both of which have unique densities owing to the presence of air or bulk OPEN ACCESS Sensors 2013, 13 6958 hydrocarbons, respectively. In order to facilitate X-ray CT imaging of other structures, a range of contrast agents have been developed to selectively identify and visualize the anatomical properties of individual tissues. Most agents incorporate atoms like iodine, gold, or barium because of their ability to absorb X-rays, and thus impart contrast to a given organ system. Here we review the strategies available to visualize lung, fat, brain, kidney, liver, spleen, vasculature, gastrointestinal tract, and liver tissues of living mice using either innate contrast, or commercial injectable or ingestible agents with selective perfusion. Further, we demonstrate how each of these approaches will facilitate the non-invasive, longitudinal, in vivo imaging of pre-clinical disease models at each anatomical site. © 2013 by the authors; licensee MDPI, Basel, Switzerland.

Gammon S.T.,University of Houston | Foje N.,Notre Dame Integrated Imaging Facility | Brewer E.M.,Emory University | Owers E.,Notre Dame Integrated Imaging Facility | And 4 more authors.
American Journal of Physiology - Lung Cellular and Molecular Physiology | Year: 2014

In vivo imaging is an important tool for preclinical studies of lung function and disease. The widespread availability of multimodal animal imaging systems and the rapid rate of diagnostic contrast agent development have empowered researchers to noninvasively study lung function and pulmonary disorders. Investigators can identify, track, and quantify biological processes over time. In this review, we highlight the fundamental principles of bioluminescence, fluorescence, planar X-ray, X-ray computed tomography, magnetic resonance imaging, and nuclear imaging modalities (such as positron emission tomography and single photon emission computed tomography that have been successfully employed for the study of lung function and pulmonary disorders in a preclinical setting. The major principles, benefits, and applications of each imaging modality and technology are reviewed. Limitations and the future prospective of multimodal imaging in pulmonary physiology are also discussed. In vivo imaging bridges molecular biological studies, drug design and discovery, and the imaging field with modern medical practice, and, as such, will continue to be a mainstay in biomedical research. © 2014 the American Physiological Society.

Sanchez F.,Polytechnic University of Valencia | Orero A.,Polytechnic University of Valencia | Soriano A.,Polytechnic University of Valencia | Correcher C.,Oncovision | And 9 more authors.
Medical Physics | Year: 2013

Purpose: The authors have developed a trimodal PETSPECTCT scanner for small animal imaging. The gamma ray subsystems are based on monolithic crystals coupled to multianode photomultiplier tubes (MA-PMTs), while computed tomography (CT) comprises a commercially available microfocus x-ray tube and a CsI scintillator 2D pixelated flat panel x-ray detector. In this study the authors will report on the design and performance evaluation of the multimodal system. Methods: X-ray transmission measurements are performed based on cone-beam geometry. Individual projections were acquired by rotating the x-ray tube and the 2D flat panel detector, thus making possible a transaxial field of view (FOV) of roughly 80 mm in diameter and an axial FOV of 65 mm for the CT system. The single photon emission computed tomography (SPECT) component has a dual head detector geometry mounted on a rotating gantry. The distance between the SPECT module detectors can be varied in order to optimize specific user requirements, including variable FOV. The positron emission tomography (PET) system is made up of eight compact modules forming an octagon with an axial FOV of 40 mm and a transaxial FOV of 80 mm in diameter. The main CT image quality parameters (spatial resolution and uniformity) have been determined. In the case of the SPECT, the tomographic spatial resolution and system sensitivity have been evaluated with a 99mTc solution using single-pinhole and multi-pinhole collimators. PET and SPECT images were reconstructed using three-dimensional (3D) maximum likelihood and ordered subset expectation maximization (MLEM and OSEM) algorithms developed by the authors, whereas the CT images were obtained using a 3D based FBP algorithm. Results: CT spatial resolution was 85 μm while a uniformity of 2.7 was obtained for a water filled phantom at 45 kV. The SPECT spatial resolution was better than 0.8 mm measured with a Derenzo-like phantom for a FOV of 20 mm using a 1-mm pinhole aperture collimator. The full width at half-maximum PET radial spatial resolution at the center of the field of view was 1.55 mm. The SPECT system sensitivity for a FOV of 20 mm and 15 energy window was 700 cpsMBq (7.8 × 10-2) using a multi-pinhole equipped with five apertures 1 mm in diameter, whereas the PET absolute sensitivity was 2 for a 350-650 keV energy window and a 5 ns timing window. Several animal images are also presented. Conclusions: The new small animal PETSPECTCT proposed here exhibits high performance, producing high-quality images suitable for studies with small animals. Monolithic design for PET and SPECT scintillator crystals reduces cost and complexity without significant performance degradation. © 2013 American Association of Physicists in Medicine.

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