Min-Sig Hwang^1,2, Katja E. Odening³, Bum-Rak Choi³, Gideon Koren³, Stephen J. Blackband^1,2, and John R. Forder^1,4
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.

Eugene Kim¹, Jiangyang Zhang², Karen Hong³, and Arvind P. Pathak^2,4
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.

Chunlei Liu^1,2, Wei Li¹, and G. Allan Johnson^2
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.

Francesca C Norris^1,2, Jon O Cleary^1,3, Joanne Henderson⁴, Benjamin Sinclair^1,5, Karen McCue⁶, Jack A Wells¹, Sebastien Ourselin⁷, Paolo Salomoni⁴, Peter J Scambler⁶, and Mark F Lythgoe^1
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.

Andrey V Demyanenko¹, Shuyi Nie¹, Yun Kee¹, Marianne Bronner-Fraser¹, and Julian Michael Tyszka^1
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.

Eric Chuan Qin¹, Ralph Sinkus², Caroline Rae¹, and Lynne Eckert Bilston^1
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 Schregel^1,2, Eva Wuerfel³, Philippe Garteiser², Timur Prozorovskiy⁴, Hartmut Merz⁵, Dirk Petersen¹, Jens Wuerfel^1,6, and Ralph Sinkus^2,6
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.

Keith D Paulsen^1,2, Adam J Pattison¹, Irina M Perreard³, John B Weaver^1,3, and David W Roberts^3
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.

Sebastian Hirsch¹, Dieter Klatt¹, Sebastian Papazoglou¹, Kaspar Josche Streitberger¹, Juergen Braun², and Ingolf Sack^1
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.

David Andrew Olsen¹, Pengfei Song¹, Kevin J Glaser¹, and Richard L Ehman^1
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.