ISMRM 24th Annual Meeting & Exhibition • 07-13 May 2016 • Singapore

Scientific Session: Diffusion: Probing Microstructure

Wednesday, May 11, 2016
Room 324-326
13:30 - 15:30
Moderators: Julien Cohen-Adad, Benoit Scherrer

What dominates the diffusivity time dependence transverse to axons: Intra- or extra-axonal water?
Hong-Hsi Lee1, Jelle Veraart1,2, Dmitry S. Novikov1, and Els Fieremans1
1New York University, Center for Biomedical Imaging, New York, NY, United States, 2iMinds-Vision Lab, University of Antwerp, Antwerp, Belgium
Diffusion MRI enables to evaluate microstructure at the mesoscopic scale. In particular, tuning the diffusion time over a wide range could increase the sensitivity for acquiring useful biomarkers, such as the axonal diameter or density. However, it is unclear whether either intra-, or extra-axonal water attribute most to the observed changes of diffusion signal with diffusion time. Here, we evaluate the dependence of the diffusion coefficient (obtained from the diffusion signal at low $$$b$$$-value) on $$$\delta$$$ and $$$\Delta$$$ in the direction perpendicular to axons in the human brain, and explain these dependencies by diffusion of water in the extra-axonal space.

Impact of transcytolemmal water exchange on quantitative characterization of tissue microstructure using diffusion MRI
Hua Li1, Xiaoyu Jiang1, Jingping Xie1, John C Gore1, and Junzhong Xu1
1Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, United States
Current diffusion MRI methods that quantitatively characterize tissue microstructure usually assume a zero transcytolemmal water exchange rate $$$\tau_{in}$$$ between intra- and extracellular spaces. This assumption may not be true in many cases of interest. The present work used both computer simulations and cell culture in vitro to investigate the influence of $$$\tau_{in}$$$ on the accuracy of fitted microstructural parameters such as mean cell size $$$d$$$, intracellular water fraction $$$f_{in}$$$ and diffusion coefficient $$$D_{in}$$$. Results indicate $$$d$$$ is relatively insensitive to $$$\tau_{in}$$$, while $$$f_{in}$$$ is always underestimated with finite $$$\tau_{in}$$$. $$$D_{in}$$$ can be fit reliably only when short diffusion times are used.  

Low frequency oscillating gradient spin-echo sequences improves sensitivity to axon diameter – an experimental validation study in live nerve tissue
Lebina Shrestha Kakkar1, Oscar Bennett1, David Atkinson2, Bernard Siow3, James Phillips4, Simon Richardson3, Enrico Kaden1, and Ivana Drobnjak1
1Centre for Medical Image Computing, University College London, London, United Kingdom, 2Centre for Medical Imaging, University College London, London, United Kingdom, 3Centre for Advanced Biomedical Imaging, University College London, London, United Kingdom, 4Department of Biomaterials & Tissue Engineering, University College London, London, United Kingdom
In a recent simulation study, Drobnjak et al demonstrates that low-frequency oscillating gradient spin-echo (OGSE) sequence is more sensitive to axon diameter than conventional pulsed gradient spin-echo (PGSE) sequence when fibre orientation is unknown or when fibre dispersion exists. Here, we experimentally validate this claim. We image a live rat sciatic nerve tissue using both sequences and compare its agreement with histology. Our results confirm that OGSE provides more accurate and precise diameter estimates compared to PGSE. Additionally, OGSE parameter estimates are less affected by reduced number of diffusion gradient directions, suggesting their use could translate into faster scan times.

Asymmetries of the dendrite density in cortical areas assessed by diffusion MR microscopy using NODDI
Achille Teillac1,2,3, Sandrine Lefranc2,3,4, Edouard Duchesnay2,3,4,5, Fabrice Poupon2,3,4, Maite Alaitz Ripoll Fuster1,2,3, Denis Le Bihan1,2,3, Jean François Mangin2,3,4,5, and Cyril Poupon1,2,3,5
1CEA NeuroSpin / UNIRS, Gif-sur-Yvette, France, 2Université Paris-Saclay, Orsay, France, 3France Life Imaging, Orsay, France, 4CEA NeuroSpin / UNATI, Gif-sur-Yvette, France, 5, Gif-sur-Yvette, France
In this study, we investigated the dendrite density in cortical areas with diffusion MR microscopy using the NODDI model and showed, on a population of healthy volunteers, significant differences between left and right hemisphere, correlated with their supported brain functions.

Diffusion-Relaxation Correlation Spectroscopic Imaging (DR-CSI): An Enhanced Approach to Imaging Microstructure
Daeun Kim1, Joong Hee Kim2, and Justin P Haldar1
1Department of Electrical Engineering, University of Southern California, Los Angeles, CA, United States, 2Department of Neurology, Washington University, St. Louis, MO, United States
We propose a new MR experiment called diffusion-relaxation correlation spectroscopic imaging (DR-CSI).  DR-CSI acquires imaging data across a range of different b-value and echo time combinations, and then performs regularized reconstruction to generate a 2D diffusion-relaxation correlation spectrum for every voxel.  The peaks of this spectrum correspond to the different tissue microenvironments that are present within each macroscopic imaging voxel, which provides powerful insight into the tissue microstructure. Compared to standard relaxometry or diffusion imaging, DR-CSI provides unique capabilities to resolve tissue compartments that have similar relaxation or diffusion parameters.  DR-CSI is demonstrated with spinal cord traumatic injury MRI data.

Linear Multi-scale Modeling of diffusion MRI data: A framework for characterization of orientational structures across length scales
Barbara Wichtmann1,2, Susie Huang1, Qiuyun Fan1, Thomas Witzel1, Elizabeth Gerstner3, Bruce Rosen1, Lothar Schad2, Lawrence Wald1,4, and Aapo Nummenmaa1
1A. A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, MA, United States, 2Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, 3Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, 4Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA, United States
We propose a new analysis technique called Linear Multi-scale Modeling (LMM) for diffusion MRI data that enables detailed microstructural tissue characterization by separating orientation distributions of restricted and hindered diffusion water compartments over a range of length scales. We demonstrate the ability of LMM to estimate volume fractions, compartment sizes and orientation distributions utilizing both simulations as well as empirical data from one healthy subject and one tumor patient acquired using a human 3T MRI scanner equipped with a 300mT/m gradient system. Possible applications of our modeling framework include characterization of diffusion microstructural signatures of pathological vs. healthy tissue.

Microscopic Interpretation and Generalization of the Bloch-Torrey Equations for Diffusion MR
Inbar Seroussi1, Ofer Pasternak1,2, and Nir Sochen 1
1Tel-Aviv university, Tel Aviv, Israel, 2Psychiatry and Radiology, Harvard Medical School, Boston, MA, United States
How to bridge microscopic molecular motion with macroscopic diffusion MR signal? We suggest a simple stochastic microscopic model for molecular motion within a magnetic field. We derive the Fokker-Planck equation of this model, which is an analytic expression of the probability density function describing the magnetic diffusion propagator. This propagator is a crucial quantity and provides the link between the microscopic equations and the measured MR signal. Using the propagator we derive a generalized version for the macroscopic Bloch-Torrey equation. The advantage of this derivation is that it does not require assumptions such as constant diffusion coefficient, or ad-hoc selection of a propagator. In fact, we show that the generalized Bloch-Torrey equations have an additional term that was previously neglected and accounts for spatial varying diffusion coefficient. Including this term better predicts MR signal in complex microstructures, such as those expected in most biological experiments.

Estimating the axon diameter from intra-axonal water diffusion with arbitrary gradient waveforms: Resolution limit in parallel and dispersed fibers
Markus Nilsson1, Samo Lasic2, Daniel Topgaard3, and Carl-Fredrik Westin4
1Lund University Bioimaging Center, Lund University, Lund, Sweden, 2CR Development AB, Lund, Sweden, 3Physical Chemistry, Lund University, Lund, Sweden, 4Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
The use of non-conventional gradient waveforms has brought renewed interest in non-invasive estimation of the axon diameter from diffusion MRI. Using conventional single diffusion encoding (SDE) at clinical MRI scanners, axons smaller than the resolution limit (4-5 microns) were indistinguishable from each other. We here predict the resolution limit for arbitrary gradient waveforms in systems with (i) parallel axons and (ii) orientation dispersion. Results show that SDE is optimal for parallel fibers, but that multiple diffusion encodings (MDE) are preferred where there is orientation dispersion. With 300 mT/m and MDE, the resolution limit was 2.8 microns for dispersed fibers.

Quantification of anisotropy and directionality in three-dimensional electron microscopy images and diffusion tensor imaging of injured rat brain
Raimo A. Salo1, Ilya Belevich2, Eppu Manninen1, Eija Jokitalo2, Olli Gröhn1, and Alejandra Sierra1
1Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland, 2Institute of Biotechnology, University of Helsinki, Helsinki, Finland
Diffusion tensor imaging (DTI) is a widely used tool, however, the contribution of brain tissue microstructure into DTI contrast is not fully understood. In this work, we propose using serial block-face scanning electron microscopy (SBEM) and Fourier analysis to gain insight into this contribution. We calculated anisotropy and orientation from SBEM stacks and compare the values to fractional anisotropy and orientation from in vivo and ex vivo DTI. This work will give new insights to the contribution of microstructure to DTI contrast in normal brain and during pathology.

A new paradigm to assess brain cell microstructure by diffusion-weighted magnetic resonance spectroscopy: proof of concept and initial results in the macaque brain
Marco Palombo1,2, Clémence Ligneul1,2, Chloé Najac1,2, Juliette Le Douce1,2, Julien Flament1,2, Carole Escartin1,2, Philippe Hantraye1,2, Emmanuel Brouillet1,2, Gilles Bonvento1,2, and Julien Valette1,2
1CEA/DSV/I2BM/MIRCen, Fontenay-aux-Roses, France, 2CNRS Université Paris-Saclay UMR 9199, Fontenay-aux-Roses, France
We introduce a novel paradigm for non-invasive brain microstructure quantification, where original diffusion modeling is merged with cutting-edge diffusion-weighted spectroscopy (DW-MRS) experiments to capture features of cellular morphology that have remained largely ignored by DW-MRI. A compact description of long-range cellular morphology is used to randomly generate large collections of synthetic cells where particles diffusion is simulated. After investigating model robustness, we apply it on metabolite ADC measured in vivo in the monkey brain up to td=2 seconds. The new paradigm introduced here opens new possibilities to non-invasively extract quantitative information about cell size, complexity and heterogeneity in the brain.

The International Society for Magnetic Resonance in Medicine is accredited by the Accreditation Council for
Continuing Medical Education to provide continuing medical education for physicians.