Brain Microstructure & Diffusion Imaging
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Monday May 9th
Room 710B  11:00 - 13:00 Moderators: Valerij Kiselev and Eleftheria Panagiotaki

11:00 74.   Axon diameter mapping in the presence of orientation dispersion using diffusion MRI  
Hui Zhang1, Penny L Hubbard2, Geoff J M Parker2, and Daniel C Alexander1
1University College London, London, United Kingdom, 2Manchester Academic Health Sciences Centre, Manchester, United Kingdom

Axon diameter mapping using diffusion MRI provides more specific biomarkers than DTI indices. Earlier works assume a model of strictly parallel axons. However, such approximation is inadequate for most white matter regions in which axons fan or bend, resulting in significant orientation dispersion. Such dispersion, if unaccounted for, leads to overestimation of axon diameters. We ameliorates this problem by proposing a model that captures orientation dispersion explicitly. We demonstrate that recovery of axon diameters is possible even in the presence of orientation dispersion, supporting accurate axon diameter mapping in a much wider set of white matter than previously possible.

11:12 75.   Magnetic Resonance Characterization of General Compartment Size Distributions  -permission withheld
Evren Ozarslan1,2, Noam Shemesh3, Cheng Guan Koay1,4, Yoram Cohen3, and Peter Joel Basser1
1STBB / PPITS / NICHD, National Institutes of Health, Bethesda, MD, United States, 2Center for Neuroscience and Regenerative Medicine, USUHS, Bethesda, MD, United States, 3School of Chemistry, Tel Aviv University, Tel Aviv, Israel, 4Department of Medical Physics, University of Wisconsin, Madison, WI, United States

Previous methods to determine the axon diameter distribution (ADD) from MR data assume a known statistical distribution of compartment sizes. To overcome this limitation, theoretical relationships between the MR signal intensity and the moments of a general distribution of cylindrical compartments are established. A one-dimensional simple harmonic oscillator based reconstruction and estimation (1D-SHORE) framework was used as a numerical tool to estimate these moments. Results on simulated and real MR data obtained from controlled water-filled microcapillaries demonstrate the power of this approach to create contrast based not only on the mean compartment size but also its variance.

11:24 76.   AxCaliber 3D 
Daniel Barazany1, Derek Jones2, and Yaniv Assaf1
1Neurobiology, Tel aviv university, Tel Aviv, Israel, 2CUBRIC, School of Psychology, Cardiff University, Wales, UK

So far, the ability to map the axon diameter distribution (ADD) along a given pathway was only possible with AxCaliber if the fiber orientation was known and so this precludes any tract-specific assessment. We extended the AxCaliber framework to 3D, and were able to achieve the ADD in any voxel of the brain and any fiber orientation. In the work, we analyzed the two main fiber fascicles of the porcine spinal cord which are known to have different ADDs. AxCaliber was able to distinguish between them and calculate their ADDs.

11:36 77.   Inferring micron-scale tissue structure using extreme value theory for cylindrically-restricted diffusion 
Leigh A. Johnston1,2, David Wright2, Rick H.H.M. Philipsen3, Scott C. Kolbe2, James A. Bourne4, Iven M.Y. Mareels1, and Gary F. Egan2
1Electrical and Electronic Engineering and NICTA VRL, University of Melbourne, Parkville, VIC, Australia, 2Howard Florey Institute, Florey Neuroscience Institutes, Parkville, VIC, Australia, 3Technical University of Eindhoven, Netherlands, 4Australian Regenerative Medicine Institute, Monash University, Australia

The non-exponential signal decay observed in q-space diffusion acqusitions is derived for restricted diffusion in cylinders, using a probabilistic approach based on extreme value theory and expectation over continuum distributions for geometry-dependent apparent diffusion coefficients. Simulation and experimental results demonstrate the accuracy of the resultant non-exponential signal decay and the ability to infer axon densities without need for pulse duration or diffusion time approximations.

11:48 78.   Activation Energies for Water Diffusion in ex-vivo White Matter 
Bibek Dhital1, Christian Labadie1,2, Harald E M÷ller1, and Robert Turner1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, 2Laboratoire de SpectromÚtrie Ionique et MolÚculaire, UniversitÚ Claude Bernard Lyon 1, France

We made MR measurements of diffusion up to very high b-factor in excised human corpus callosum, over a wide temperature range. Above a freezing phase transition at -20 ░C, data showed a robust bi-exponential dependence on b-factor. Below this temperature only half of the slow component remained, suggesting two water pools within this component. An Arrhenius plot revealed significantly different activation energies for the fast and slow components. The lower of these corresponds well to breaking a hydrogen bond in a locally ordered region. This suggests that unfrozen water consists of hydration layers close to the membranes.

12:00 79.   Assessment of axon diameter distribution in mouse spinal cord with q-space imaging 
Henry H. Ong1, and Felix W. Wehrli1
1Laboratory for Structural NMR Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, United States

Knowledge of axon morphology would provide important insight into neural function, anatomy and pathology. Q-space imaging (QSI) offers potential for indirect assessment of WM architecture and already has been used to measure intra-cellular volume fraction and mean axon diameter. Here, we examine the feasibility of QSI to measure axon diameter distribution (ADD) from white matter tracts in healthy mouse spinal cords using the displacement probability density function. The results show that QSI-derived ADDs semi-quantitatively agree with histologic ADDs and consistently illustrate the relative differences in ADD between WM tracts.

12:12 80.   Surface-to-volume ratio with oscillating gradients 
Dmitry S Novikov1, and Valerij G Kiselev2
1Radiology, NYU School of Medicine, New York, NY, United States, 2Diagnostic Radiology, University Hospital Freiburg, Freiburg, Germany

Diffusion coefficient is known to reveal the surface-to-volume ratio of restrictions at short diffusion times. Sufficiently short diffusion times are practically achievable with the oscillating gradient technique or with the CPMG refocusing train in the presence of a static gradient. Interpetation of such measurements relies on representing the short-time diffusivity limit in the frequency domain. For both of these oscillating techniques, we derive exact expressions for the high-frequency behavior of the diffusion coefficient, applicable to probe the surface-to-volume ratio of restrictions. We also describe how to calculate the effect of restrictions for arbitrary gradient waveforms.

12:24 81.   Probing microscopic cellular architecture in the mouse brain by oscillating gradient diffusion tensor imaging 
Manisha Aggarwal1, Susumu Mori1, and Jiangyang Zhang1
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Diffusion measurements with conventional pulsed gradient diffusion MRI experiments reflect the combined effects of restriction barriers to water diffusion at multiple spatial scales, but cannot distinguish between different spatial scales. With oscillating diffusion gradients, it is possible to probe diffusion at separate spatial scales by varying the modulation frequency of the oscillating gradients. In this study, three dimensional diffusion tensor imaging (DTI) of perfusion-fixed mouse brains using oscillating diffusion-sensitizing gradients is presented. The resulting diffusion tensor spectrum D(f) revealed, for the first time, unique frequency-dependent tissue contrasts in the mouse cerebellum and hippocampus.

12:36 82.   Double-PFG MR imaging of the CNS: probing underlying grey matter microstructure 
Noam Shemesh1, Daniel Barzany2, Ofer Sadan3, Yuval Zur4, Daniel Offen5, Yaniv Assaf2, and Yoram Cohen1
1School of Chemistry, Tel Aviv University, Tel Aviv, Israel, 2Department of Neurobiology, Tel Aviv University, Israel, 3Department of Neurology, Tel-Aviv Medical Center, Tel Aviv University, Israel, 4GE Healthcare, Israel, 5Laboratory of Neurosciences, Felsenstein Medical Research Center, Department of Neurology, Rabin Medical center and Tel Aviv University, Israel

Double-Pulsed-Field-Gradient (d-PFG) MR is emerging as a useful methodology for depicting underlying microstructural information in scenarios where conventional single-PFG (s-PFG) are very limited, such as when anisotropic compartments are randomly oriented. Here, we used d-PFG MRI on phantoms, pig spinal cord and rat brain. The angular variations in the E(°) data could be easily observed for all specimens even in the raw data; furthermore, the presence of modulated E(°) plots in grey matter tissues revealed that water is diffusing in randomly oriented anisotropic compartments having different eccentricities, which appeared as different patterns within the cortex of the rat brain.

12:48 83.   A comparative study of axon diameter imaging techniques using diffusion MRI 
Hui Zhang1, Daniel Barazany2, Yaniv Assaf2, Henrik M Lundell3, Daniel C Alexander1, and Tim B Dyrby3
1University College London, London, United Kingdom, 2Tel Aviv University, Tel Aviv, Israel, 3Copenhagen University Hospital Hvidovre, Hvidovre, Denmark

Axon diameter and density provide information about the function and performance of white matter pathways. Direct measurement of such microstructure features offers more specific biomarkers than DTI indices. Many techniques to measure axon diameter statistics using diffusion MRI have been proposed in the literature, ranging from model-based approaches to Q-space imaging, but little is known of their relative performance and consistency. This work compares several representative model-based approaches quantitatively to gain insight into how the choices of tissue model and imaging protocol impact the estimation of microstructural features.