Microscopy & Elastography
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Monday May 9th
Room 513A-D  11:00 - 13:00 Moderators: Robert R. Edelman and Cornelius J. Faber

11:00 34.   Non-invasive Visualization of the Complete Cardiac Conduction System using MR Microscopy  
Min-Sig Hwang1,2, Katja E. Odening3, Bum-Rak Choi3, Gideon Koren3, Stephen J. Blackband1,2, and John R. Forder1,4
1McKnight Brain Institute, Gainesville, FL, United States, 2Neuroscience, University of Florida, Gainesville, FL, United States, 3Cardiovascular Research Center, The Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, United States, 4Radiology, University of Florida, Gainesville, FL, United States

In this study, we demonstrate that MRI at microscopic resolutions, i.e. MR microscopy (MRM), combined with high angular resolution diffusion microscopy (HARDM), can describe non-invasively the complete cardiac conduction system and anatomical features in isolated rabbit hearts, as a precurser to developing a mathematical model of depolarizaton in the heart. The combined investigative technique of MRM and HARDM is observed to be an effective method of monitoring morphological changes occurring in the cardiac conduction system.

11:12 35.   A New Method for Phenotyping the Brain Tumor Microenvironment Using MR Microscopy 
Eugene Kim1, Jiangyang Zhang2, Karen Hong3, and Arvind P. Pathak2,4
1Department of Biomedical Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD, United States, 22Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of Medicine, 3The Johns Hopkins University School of Public Health, 4JHU ICMIC Program

The development of pre-clinical brain tumor models and anti-angiogenic therapies has created a critical need to characterize the brain tumor microenvironment. Here we describe a novel method for whole-brain 3D mapping of the vasculature of a mouse brain tumor model using magnetic resonance microscopy (μMRI). The vascular architecture was characterized by six morphological parameters. Region-of-interest analysis showed significant differences in these parameters between tumor and contralateral brain. In combination with diffusion-weighted MRI, we could characterize the phenotypes of post-inoculation day-12 and day-17 tumors. These results demonstrate the feasibility of using μMRI to characterize microenvironmental changes that accompany brain tumor progression.

11:24 36.   MR Microscopy of Brain Cytoarchitecture by Quantitative Mapping of Magnetic Susceptibility 
Chunlei Liu1,2, Wei Li1, and G. Allan Johnson2
1Brain Imaging and Analysis Center, Duke University, Durham, NC, United States, 2Radiology, Duke University, Durham, NC, United States

At high field strengths, phase images showed excellent image contrast and revealed anatomic structures that were not visible on the corresponding magnitude images. Here, we demonstrate that phase images and, more importantly, the corresponding susceptibility maps provide a novel contrast mechanism to visualize the microstructure of brain anatomy at the exquisite resolution offered by MR microscopy. In particular, we believe the described technique may provide a powerful tool to visualize brain cytoarchitecture at high speed and with ultra-high spatial resolution. We further anticipate that imaging magnetic susceptibility may provide a powerful tool for studying animal models of white matter diseases.

11:36 37.   Imaging neural stem cell populations in the developing mouse brain using magnetic resonance micro histology 
Francesca C Norris1,2, Jon O Cleary1,3, Joanne Henderson4, Benjamin Sinclair1,5, Karen McCue6, Jack A Wells1, Sebastien Ourselin7, Paolo Salomoni4, Peter J Scambler6, and Mark F Lythgoe1
1Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, 2Centre for Mathematics and Physics in the Life Sciences and Experimental Biology (CoMPLEX), University College London, London, United Kingdom, 3Department of Medical Physics and Bioengineering, University College London, London, United Kingdom, 4Samantha Dickson Brain Cancer Unit, UCL Cancer Institute, London, United Kingdom, 5Centre for Medical Image Computing, University College London, London, United Kingdom, 6Molecular Medicine Unit, UCL Institute of Child Health, London, United Kingdom, 7Centre for Medical Image Computer, University College London, London, United Kingdom

Advanced methods that enable labelling of neural stem cells and progenitor cells are fundamental for investigating brain development under normal and pathological conditions. MR histology is an emergent technique that may be able to provide an array of staining options to highlight distinct cellular structures. We identify previously undetected substructures and delineate regions of neural stem cells and progenitor cells within the intact embryo brain using an MR histological stain. This methodology could enable greater sensitivity for phenotypic characterisation of mutant mouse models by highlighting specific cellular structures for investigation of developmental and disease processes.

11:48 38.   Dual-Mode Optical-MR Microscopy with Uniplanar Gradient Coils 
Andrey V Demyanenko1, Shuyi Nie1, Yun Kee1, Marianne Bronner-Fraser1, and Julian Michael Tyszka1
1Biology, California Institute of Technology, Pasadena, CA, United States

Magnetic resonance microscopy offers unique complementary information to optical microscopy in basic biological and clinical applications. The integration of optical microscopes with MR imaging hardware is becoming increasingly popular and we present here a dual-mode MR and visible light optical microscope targeted towards applications in developmental biology and embryology. The instrument consists of a uniplanar three-axis gradient module and planar RF transceiver coil with a MR-compatible CCD optical microscope focused at the center of the gradient target volume via a planar mirror. Simultaneous optical and MR imaging of live Xenopus laevis embryos resulted in images of the dorsal embryonic surface with complementary imaging of internal morphological development over periods longer than 12 hours.

12:00 39.   Investigating anisotropic elasticity using MR-Elastography combined with Diffusion Tensor Imaging: Validation using anisotropic and viscoelastic phantoms 
Eric Chuan Qin1, Ralph Sinkus2, Caroline Rae1, and Lynne Eckert Bilston1
1Neuroscience Research Australia, Randwick, NSW, Australia, 2Centre de Recherches Biomédicales, Hopital Beaujon, Paris, France

Investigating the anisotropic mechanical properties of tissue can provide additional physical parameters to detect abnormal changes in skeletal muscle diseases such as atrophy. In this study, we combined Diffusion Tensor Imaging (DTI) with MR-Elastography (MRE) to probe the anisotropic elasticity of viscoelastic materials. By assuming a transversely isotropic model, the shear moduli parallel and perpendicular to the local fiber direction (provided by DTI) can be calculated. Results are presented for anisotropic viscoelastic phantoms and ex vivo bovine skeletal muscles. The MRE/DTI mechanical anisotropic ratio was compared with the “gold-standard” rotational rheometry results. No significant difference was observed between the two.

Katharina Schregel1,2, Eva Wuerfel3, Philippe Garteiser2, Timur Prozorovskiy4, Hartmut Merz5, Dirk Petersen1, Jens Wuerfel1,6, and Ralph Sinkus2,6
1Institute of Neuroradiology, University Luebeck, Luebeck, Germany, 2INSERM UMR 773, CRB3, Centre de Recherches Biomédicales Bichat-Beaujon, Paris, France,3Department of Pediatrics, University Luebeck, Luebeck, Germany, 4Molecular Neurology, Heinrich-Heine-University, Life Science Center, Duesseldorf, Germany,5Department of Pathology, University Luebeck, Luebeck, Germany, 6authors contributed equally

Magnetic Resonance Elastography (MRE) is a novel technique that directly visualizes and quantitatively measures biomechanical tissue properties in vivo. Already smallest changes of the brain parenchymal viscoelasticity, e.g. occurring during physiological brain maturation in adolescent mice, can be reliably detected. In a longitudinal study, we correlated for the first time biomechanical properties quantified in vivo by MRE with detailed histopathology of brain parenchymal alterations in healthy C57bl/6 mice and in a mouse model of multiple sclerosis. MRE correlated with the degree of myelination as well as with extracellular matrix integrity, but not with cellular infiltration into the brain parenchyma.

12:24 41.   Hydrocephalus detection using intrinsically-activated MRE 
Keith D Paulsen1,2, Adam J Pattison1, Irina M Perreard3, John B Weaver1,3, and David W Roberts3
1Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States, 2Norris Cotton Cancer Center, Lebanon, New Hampshire, United States,3Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, United States

Hydrocephalus is a disease in which cerebrospinal fluid is obstructed causing an increase in ventricular size and, in some cases, an increased intracranial pressure. Current imaging modalities only detect oversized ventricles, which can be confused with cerebral atrophy, a disease where enlargement occurs due to shrinkage of the periventricular parenchyma. Magnetic resonance elastography (MRE) may differentiate between these two categories of disease based on mechanical property differences. A previously described ‘intrinsic activation’ MRE method was applied to a series of normal and hydrocephalic patients. Initial results are promising and show significant differences in stiffness and pore-pressure estimations between the two patient groups.

12:36 42.   Cerebral MR elastography for measuring poroelastic properties of the brain 
Sebastian Hirsch1, Dieter Klatt1, Sebastian Papazoglou1, Kaspar Josche Streitberger1, Juergen Braun2, and Ingolf Sack1
1Department of Radiology, Charité - University Medicine Berlin, Berlin, Germany, 2Institute of Medical Informatics, Charité - University Medicine Berlin, Berlin, Germany

Cerebral MR poroelastography based on multi-slice echo planar imaging is introduced. The method allows for acquisition of full time-resolved 3D-wave fields with 30 slices in 3 min. Gated data acquisition by pulse wave trigger is demonstrated. Two complex mechanical moduli corresponding to Lamé's coefficients are recovered using a direct 3D-harmonic field inversion. While one coefficient corresponds to the shear modulus measured in previous studies of 2D cerebral MRE, the other is related to dilatational deformation occurring in biphasic soft tissue and is thus determined by microscopic fluid filtration.

12:48 43.   Cardiac-Gated Hepatic MR Elastography with Intrinsic Transient Waveforms  -permission withheld
David Andrew Olsen1, Pengfei Song1, Kevin J Glaser1, and Richard L Ehman1
1Mayo Clinic, Rochester, Minnesota, United States

In conventional MR elastography (MRE), an external vibration source generates harmonic waves to characterize tissue. In this study, we developed and evaluated a dynamic MRE method for quantifying liver stiffness using intrinsic transient waveforms imparted on the liver by the beating heart by synchronizing motion-encoding gradients to the cardiac cycle. Sixteen subjects were imaged with conventional harmonic and cardiac-gated transient MRE. The results show that this method is reproducible and gives quantitative stiffness values that approximate those obtained with conventional MRE and may allow for the eventual screening of patients with liver disease using standard MRI equipment.