Valerij Kiselev

Regimes of diffusion weighting are discussed starting with the simplest measurement with narrow gradient pulses. Such measurements can be classified on a plane of diffusion time and the wave vector induced by the diffusion-sensitizing gradients. Beyond this simple picture are gradients with a finite duration, which radically change the signal behavior for the closed compartment. Versatile diffusion weighting scheme, the successors of the double diffusion encoding, are discussed under the overarching idea of geometry matching between the gradient encoding and the targeted cell population. 

Joseph Ackerman

This didactic lecture will highlight illustrative measurements with physically-realizable model systems that provide simplifying parsimonious dMRI test platforms and deliver parameters useful for the modeling of microstructurally-complex real tissues.  These dMRI test platforms will include: (i) perfused, cultured (in vitro), microbead-adherent HeLa cells; (ii) perfused, cultured (in vitro), microbead-adherent neurons and glia (aka, “brains-on-beads”); (iii) Xenopus laevis oocyte (aka, frog egg); and (iv) intracellular N-acetylaspartate (NAA) in rat brain in vivo.

Junzhong Xu¹, Xiaoyu Jiang¹, Sean P Devan², Lori R Arlinghaus¹, Eliot T McKinley¹, Jingping Xie¹, Zhongliang Zu¹, Qing Wang³, A Bapsi Chakravarthy¹, Yong Wang³, and John C Gore^1
1Vanderbilt University Medical Center, Nashville, TN, United States, ²Vanderbilt University, Nashville, TN, United States, ³Washingon University, St. Louis, MO, United States

Non-invasive mapping of cell size distribution provides a unique means to probe biological tissues.  We introduce a diffusion MRI based framework that does not require prior assumptions on distribution functions to provide tissue microstructural properties including non-cell-volume-weighted cell size distributions. We validated this approach, which we call MRI-cytometry, comprehensively using computer simulations in silico, cultured cells in vitro, and animal xenografts in vivo. We then demonstrate the implementation of MRI-cytometry in imaging breast cancer patients using clinical 3T MRI, indicating its potential clinical application such as more specific assessments of tumor status and therapeutic responses.

Nathan Hu Williamson¹, Rea Ravin¹, Dan Benjamini¹, Hellmut Merkle², Melanie Falgairolle², Michael J O'Donovan², Dvir Blivis², Dave Ide², Teddy Cai¹, Nima Ghorashi³, Ruiliang Bai^1,4, and Peter Basser^1
1Eunice Kennedy Shriver National Institutes of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States, ²National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, United States, ³National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, United States, ⁴College of Biomedical Engineering and Instrument Science, Zhejiang University, Hangzhou, China

Diffusion and exchange methods are developed using the large static gradient produced by a single-sided permanent magnet and provide resolution to water within sub-micron membrane structures. Using tissue delipidation methods, we show that water diffusion is restricted solely by lipid membranes. Most of the diffusion signal can be assigned to water in tissue which is far from membranes. The remaining 25% can be assigned to water restricted within membrane structures at the cellular, organelle, and vesicle levels. Diffusion exchange spectroscopy measures water exchanging between membrane structures and free environments at 100 s⁻¹.

Hong-Hsi Lee¹, Qiyuan Tian², Chanon Ngamsombat², Daniel R Berger³, Jeff W Lichtman³, Susie Y Huang², Dmitry S Novikov¹, and Els Fieremans^1
1Center for Biomedical Imaging, Department of Radiology, NYU School of Medicine, New York, NY, United States, ²Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, United States, ³Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, United States

We perform for the first time Monte Carlo simulations inside realistic human intra-axonal space segmented from electron microscopy. We observe non-Gaussian time-dependent diffusion in both radial and axial directions, and validate analytical models of these phenomena. We also compare the results in human axons with similar simulations in mouse axons, and discuss how the differences in axonal parameters (mean radius, radius variation, undulations) explain the differences in the simulation results between the human and mouse.  

Marco Palombo¹, Cecile Gallea^2,3, Guglielmo Genovese^3,4, Stephane Lehericy^2,3, and Francesca Branzoli^3,4
1Centre for Medical Image Computing, Department of Computer Science, University College London, London, United Kingdom, ²Team "Movement Investigations and Therapeutics", Brain and Spine Institute - ICM, Paris, France, ³INSERM U 1127, CNRS UMR 7225, Sorbonne University, Paris, France, ⁴Brain and Spine Institute - ICM, Centre for NeuroImaging Research - CENIR, Paris, France

Diffusion-weighted magnetic resonance spectroscopy (DW-MRS) performed at ultra-high b-values enables the quantification of fine cell microstructural features such as dendritic spine density. Here, we measured in-vivo the diffusion of total N-acetyl-aspartate (tNAA) and choline compounds (tCho) in the human cerebellar and cerebral cortex at 3 T, up to a b-value of 24 ms/μm². We used biophysical modelling and numerical simulations to interpret the metabolite signal attenuation with the b-value. The diffusion of tNAA, a mostly neuronal metabolite, is compatible with a larger presence of spines and highly restricting granular cell soma in cerebellar compared to cerebral cortex. 

Mélissa Vincent^1,2, Mylène Gaudin^1,2, Covadonga Lucas-Torres³, Océane Guillemaud^1,2, Carole Escartin^1,2, Alan Wong³, and Julien Valette^1,2
1Molecular Imaging Research Centre (MIRCen), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Fontenay-aux-Roses, France, ²UMR 9199, Neurodegenerative Diseases Laboratory, Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud, Université Paris-Saclay, Fontenay-aux-Roses, France, ³NIMBE/ Laboratoire de Structure et Dynamique par Résonance Magnétique (LSDRM), Commissariat à l'Energie Atomique et aux Energies Alternatives (CEA), Gif-sur-Yvette, France

Diffusion in the extracellular space is assessed by state-of-the-art diffusion-weighted MRS techniques following intracerebral injection of sucrose, which predominantly remains in the extracellular space. Sucrose diffusion appears to be not strictly Gaussian and different from intracellular metabolites diffusion. Signal attenuation is stronger and deviates from mono-exponential attenuation at very high b-values, suggesting the presence of some highly restricted pool. The ADC is higher and decreases when augmenting t_d, indicating that the tortuosity regime is not reached yet. Lastly, unlike intracellular metabolites, sucrose diffusion does not exhibit microstructural anisotropy in double-diffusion-encoding experiments.