Morphologic Phenotyping with MR Microscopy: The Visible Mouse

Johnson, G. Allan; Cofer, Gary P.; Gewalt, Sally L.; Hedlund, Laurence W.

doi:10.1148/radiol.2223010531

Cited by 236 publications

(189 citation statements)

References 16 publications

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“…With these scanners it is possible to acquire images with a spatial resolution down to 25 micrometers (27). However, with increasing magnetic field strength, magnetic susceptibility artifacts become a major problem and specialized pulse sequence design is required (28).…”

Section: Discussionmentioning

confidence: 99%

High‐resolution three‐dimensional MR angiography of rodent tumors: Morphologic characterization of intratumoral vasculature

Fink

Kießling

Bock

et al. 2003

Magnetic Resonance Imaging

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Purpose:To evaluate high-resolution three-dimensional MR angiography (MRA) for the visualization and morphologic characterization of intratumoral vasculature. Materials and Methods:Two subcutaneous rodent tumor models (human skin carcinoma HaCaT-ras-A-5RT3 grown in nude mice and rat prostate carcinoma R3327-AT1 grown in Copenhagen rats) were examined with a clinical 1.5 T MR-system. For MRA a dedicated high-resolution threedimensional gradient echo pulse sequence with a voxel size of 166 ϫ 206 ϫ 320 m 3 was performed after injection of Gadomer-17. The image analysis included a correlation of intratumoral vessels with histology. Signal intensity measurements were performed in the vena cava, the tumor underlying muscle, and in various regions of the tumor. Signal-to-noise-ratios (SNR) and contrast-to-noise-ratios (CNR) were calculated from this measurement.Results: High-resolution MRA allowed a clear distinction of intratumoral blood vessels. The mouse tumor model tended to be strongly vascularized with several intratumoral blood vessels clearly displayed by MRA. When correlated with histology, these intratumoral blood vessels had a size in the range of 300 to 400 m. In contrast, rat tumors had only sparse capillary intratumoral blood vessels that could only be demonstrated by histology. In both tumor models, dilated blood vessels were observed in the subcutaneous tissue near the tumor. In general, areas with a strong contrast enhancement correlated with viable, well vascularized tumor regions, whereas non-enhancing tumor areas correlated with tumor necrosis or hypoxic areas. Conclusion:High-resolution three-dimensional MRA allows the visualization of intratumoral vasculature in rodent models. With minimal hardware and software modifications, high-resolution MRA could be performed on a clinical 1.5 T MRI scanner. Morphologic characterization of intratumoral blood vessels could add important insights into the process of tumor angiogenesis.

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Section: Discussionmentioning

confidence: 99%

High‐resolution three‐dimensional MR angiography of rodent tumors: Morphologic characterization of intratumoral vasculature

Fink

Kießling

Bock

et al. 2003

Magnetic Resonance Imaging

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“…The requirements for increased spatial resolution acquisitions (of orders matching cellular size of approximately 100-200 μm 3 ) led to fast switching, high-amplitude (up to 1000 mT/m), high-slew rate (up to 11250 mT/s) gradients (exhibiting linearity of better than ±3-5%/mm) for ex-vivo constructions of atlases [Johnson 2002] or in-vivo high-resolution isotropic cardiac imaging [Bucholz 2008, Perperidis 2011. Often associated with extra inserts (of approximately 6-20 cm in inner diameter), such gradients impose further spatial restrictions in animal placement and monitoring during cardiac imaging.…”

Section: Gradient Coil Technologymentioning

confidence: 99%

Study of the Murine Cardiac Mechanical Function Using Magnetic Resonance Imaging: The Current Status, Challenges, and Future Perspectives

Constantinides¹

2013

Practical Applications in Biomedical Engineering

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Despite the existence of a plethora of cardiac functional techniques for characterization of mechanical structure, function and dysfunction, a parallel need exists for development of invasive and non-invasive tools and techniques to describe the left ventricular (LV) tissue material properties as these relate to the: (a) mechanical pumping function of the LV; (b) myocardial oxygen demand defining myocyte metabolic status; (c) coronary blood flow and its auto-regulation; (d) arhythmogenic risk; (e) cell-signaling pathways responsible for growth and remodeling during development and disease. Reinforcing basic physiology work, invasive catheterization experiments ] have also allowed determination of inotropic and lusitropic cardiac status, while Magnetic Resonance Imaging (MRI) experimentation, methodologies and technology advances have facilitated migration of such work to a non-invasive imaging platform, with tremendous potential for future basic science and translational research.Specifically, advances in MRI techniques (myocardial spin tagging [Zerhouni 1988, Axel 1989, DENSE [Aletras 1999], and harmonic phase imaging [Osman 1999]) have been introduced over the last decades to quantify cardiac function, allowing myocardial tracking, motion and strain quantification in normal and genetically engineered mice [Rockman 1991, Franco 1999, Brede 2001, Engel 2004, Wilding 2005. Critical to such work has been the validation of the underlying hypothesis of morphological and functional scaling from mouse to human (through consideration of global cardiac function, circulatory control, blood flow distribution, Ca 2+ storage and cycling, myosin light chain distribution, and force frequency reserve), for comparative studies.This chapter provides an overview of the major physiological issues and challenges for mouse MR imaging and discusses the most recent and major advances in conventional and new cardiac Magnetic Resonance imaging strategies, that ultimately allow quantification of motion, global, and regional cardiac function, strain, and elasticity, characterizing inotropic and lusitropic contractile function and dysfunction in humans and transgenic mice for image-based phenotyping.Specifically, this chapter attempts a detailed reference to the mouse as a research model, focusing on its genetic background and homology with the human genome and to the developmental and morphological differences between mouse and man, thus addressing cellular and global organ similarities and differences. As a basic determinant of structure, cardiac functional differences are associated, justified by carefully-controlled indices that determine integrative physiological control and functional activities, including metabolism, perfusion, angiogenetic, collateral flow, and coronary reserve. The importance and impact of anesthesia for image-based phenotyping in patho-physiological status is addressed with brief references to the possible mechanisms and cellular and sub-cellular target sites of anesthesia action. The section is complemented with...

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“…Active staining, first described by Johnson et al in 2002(Johnson et al, 2002b [Bracco Diagnostics, Princeton, NJ]) have been explored with wide variation of application methods (immersion, transcardial perfusion) and varied concentrations. The method of choice for the mouse brain uses a series of perfusing solutions administered via a transcardial approach.…”

Section: Fixation/stainingmentioning

confidence: 99%

High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology

et al. 2007

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The Mouse Bioinformatics Research Network (MBIRN) has been established to integrate imaging studies of the mouse brain ranging from three-dimensional (3D) studies of the whole brain to focused regions at a sub-cellular scale. Magnetic resonance (MR) histology provides the entry point for many morphologic comparisons of the whole brain. We describe a standardized protocol that allows acquisition of 3D MR histology (43-micron resolution) images of the fixed, stained mouse brain with acquisition times < 30 minutes. A higher-resolution protocol with isotropic spatial resolution of 21.5 microns can be executed in 2 hours. A third acquisition protocol provides an alternative image contrast (at 43-micron isotropic resolution), which is exploited in a statistically driven algorithm that segments 33 of the most critical structures in the brain. The entire process, from specimen perfusion, fixation and staining, image acquisition and reconstruction, post-processing, segmentation, archiving, and analysis is integrated through a structured workflow. This yields a searchable database for archive and query of the very large (1.2 GB) images acquired with this standardized protocol. These methods have been applied to a collection of both male and female adult murine brains ranging over 4 strains and 6 neurologic knockout models. This collection and acquisition methods are now available to the neuroscience community as a standard web-deliverable service.

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Morphologic Phenotyping with MR Microscopy: The Visible Mouse

Cited by 236 publications

References 16 publications

High‐resolution three‐dimensional MR angiography of rodent tumors: Morphologic characterization of intratumoral vasculature

High‐resolution three‐dimensional MR angiography of rodent tumors: Morphologic characterization of intratumoral vasculature

Study of the Murine Cardiac Mechanical Function Using Magnetic Resonance Imaging: The Current Status, Challenges, and Future Perspectives

High-throughput morphologic phenotyping of the mouse brain with magnetic resonance histology

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