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Keywords: White Matter, Tractography & Fibre Modelling

Mapping neuronal trajectories requires accurate determination of fiber crossings. Diffusion MRI detects fiber orientations but is affected by multiple brain structures and requires constant validation. Small-angle X-ray scattering (SAXS) can specifically image myelinated axons exploiting myelin’s periodic nanostructure. However, its capability to detect crossing fibers is still unexplored. We show that SAXS detects multiple crossing fibers using human corpus callosum strips, and in white and gray matter of mouse, vervet monkey, and human brain.  We compare results to polarized light and tracer experiments and show that SAXS more sensitively detects fiber crossings compared to diffusion MRI on the same samples.

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Benjamin Ades-Aron¹, Valentin Stepanov¹, Santiago Coelho¹, Alon Mogilner², Dmitry S. Novikov¹, Timothy M. Shepherd¹, and Els Fieremans^1
1Radiology, Center for biomedical imaging, NYU Grossman School of Medicine, New York, NY, United States, ²Neurosurgery, NYU Grossman School of Medicine, New York, NY, United States

Keywords: White Matter, Data Analysis, high-resolution, visualization

In vivo visualization and quantitative assessment of small anisotropic brain structures is challenging with diffusion MRI because of signal-to-noise limitations. We show that direct visualization of small structures, like the fornix or stria medullaris, dramatically improves using denoised 1-mm isotropic resolution complex-valued dMRI data. This approach also reduces the bias and variance of diffusion parameter estimations for small structures. Increased resolution with denoising decreases parameter variance due to thermal noise and partial volume effects – these data also can be used to better estimate the true biological variance in a structure by extrapolating the data to the infinite SNR limit.

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Maelig Chauvel¹, Ivy Uszynski¹, Marco Pascucci¹, Bastien Herlin¹, Yann Leprince², Jean-François Mangin¹, William Hopkins³, and Cyril Poupon^1
1Université Paris-Saclay, CEA, CNRS, UMR 9027, BAOBAB, NeuroSpin , Gif-sur-Yvette, France, Saclay, France, ²UNIACT, NeuroSpin, Université Paris-Saclay, CNRS, CEA, Gif-sur-Yvette, France, Saclay, France, ³Michele E Keeling Center for Comparative Medicine and Research, The University of Texas MD Anderson Cancer Center, Bastrop, Texas, TX, United States

Keywords: White Matter, Brain Connectivity, chimpanzee, white matter atlas

Humans and chimpanzees are related by a common ancestor that lived around 6 to 7 millions years ago. From then, a cascade of acquired brain features have occurred and the scientific community has tried for years to capture them. Providing measures of the hominin brain divergences or conserved characters can be challenging considering the multitude of variables involved. We propose here a study relying on an intuitive and yet innovative morphological analysis of the deep white matter (DWM) bundles of the human and chimpanzee brain using isomap algorithm.

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Soo Hyun Shin¹, Dina Moazamian¹, James Lo^1,2, Hyungseok Jang¹, Michael Carl³, Eric Y. Chang^1,4, Jiang Du^1,2,4, and Yajun Ma^1
1Department of Radiology, University of California, San Diego, La Jolla, CA, United States, ²Department of Bioengineering, University of California, San Diego, La Jolla, CA, United States, ³GE Healthcare, San Diego, CA, United States, ⁴Radiology Service, Veterans Affairs San Diego Healthcare System, La Jolla, CA, United States

Keywords: White Matter, Contrast Mechanisms

Demyelination is a common hallmark of neurodegenerative diseases such as multiple sclerosis. Thus, selective imaging of myelin will greatly enhance the diagnosis of such diseases. Here, we demonstrate the feasibility of acquiring whole-brain 3D myelin water phase maps via short-TR adiabatic inversion recovery (STAIR) MRI. The phase of proton density-weighted (PD) images was subtracted from the phase of STAIR images to remove the background field. The overall positive frequency shift, with a larger shift in the splenium of the lower slice, matches the white matter fiber orientation.

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Sarah Rosemary Morris^1,2,3, Irene M. Vavasour^3,4, Anastasia Smolina^5,6, Erin MacMillan^4,7, Guillaume Gilbert⁷, Michelle Lam^1,4, Piotr Kozlowski^1,2,3,4, Carl A. Michal¹, Alan Manning¹, Alex L. MacKay^1,3,4, and Cornelia Laule^1,2,3,4,8
1Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada, ²International Collaboration on Repair Discoveries, Vancouver, BC, Canada, ³Radiology, University of British Columbia, Vancouver, BC, Canada, ⁴UBC MRI Research Centre, Vancouver, BC, Canada, ⁵Medical Biophysics, University of Toronto, Toronto, ON, Canada, ⁶The Hospital for Sick Children, Toronto, ON, Canada, ⁷MR Clinical Science, Philips Healthcare Canada, Markham, ON, Canada, ⁸Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada

Keywords: White Matter, CEST & MT, inhomogeneous Magnetization Transfer, ihMT, myelin water fraction, MWF, magnetization transfer, MT, fibre direction, orientation dependence, diffusion tensor imaging (DTI), myelin

We measured MTR, ihMTR, MWF and fibre orientation from DTI in 17 white matter regions in 17 healthy adults at 3 T. All three metrics showed an apparent orientation dependence: MWF and ihMTR were lower in fibres perpendicular to B₀ by 6% and 1% respectively compared to those parallel, while MTR was lower by 0.5% at ~40°, with the highest values in fibres perpendicular to B₀. However, separating the apparent orientation dependence by region revealed large variation in the trends, suggesting that real differences in myelination and other microstructural properties are confounding the apparent orientation dependence measured using this method.

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Keywords: White Matter, Diffusion Tensor Imaging, 7T MRI, Tractography, Connectivity, Postmortem

Diffusion-tensor imaging (DTI) is routinely used to estimate the pattern, orientation, and directionality of white matter tracts in human living subjects. However, diffusion imaging of ex-vivo brain specimens is complex due to the diffusivity properties of fixed brain tissue. We developed a novel methodology for tractography of a 1-week postmortem fixed human brainstem and cerebellum specimen utilizing a deterministic fiber tracking algorithm on a 7T MR DTI diffusion scheme registered to an MNI space through landmark-based affine registration. The results showed highly detailed tractography images and agreement between left and right crossing and non-crossing fibers.

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Tyler D. Robinson¹, Yutong L. Sun¹, Paul T. H. Chang¹, and J. Jean Chen^1,2,3
1Rotman Research Institute, Baycrest, Toronto, ON, Canada, ²Medical Biophysics, University of Toronto, Toronto, ON, Canada, ³Biomedical Engineering, University of Toronto, Toronto, ON, Canada

Keywords: White Matter, Perfusion

This study examined baseline and age-related differences in white matter perfusion and microstructural integrity across ten tracts of interest using 535 adult subjects of the Human Connectome Project in Aging. Whole-brain and tractwise relationships were identified between age, cerebral blood flow, mean diffusivity, and fractional anisotropy. Additionally, regional differences in age-related perfusion and microstructural trajectories were identified, representing one of the first direct examinations of regional variation in white matter perfusion in aging.

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John Laporte¹, Mary Faulkner¹, Zhaoyuan Gong¹, Maryam Alsameen¹, Mohammad A.B.S Akhonda¹, Curtis Triebswetter¹, Matthew Kiely¹, and Mustapha Bouhrara^1
1Laboratory of Clinical Investigations, National Institute on Aging, Baltimore, MD, United States

Keywords: White Matter, Relaxometry

Hypertension is a major risk factor for a myriad of neurodegenerative diseases. However, the effect of hypertension on cerebral microstructure, especially myelination, remains poorly understood. We employed multicomponent MR relaxometry and DTI to investigate the association between hypertension and cerebral microstructural integrity, with a focus on myelin content, in a cohort of cognitively unimpaired adults. Our results indicate that adults with hypertension exhibit significantly lower cerebral microstructural integrity and axonal myelination as compared to controls across, several white matter structures.

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Rona Shaharabani¹ and Aviv Mezer^1
1Edmond & Lily Safra Center for Brain Science, The Hebrew University, Jerusalem, Israel

Keywords: White Matter, Multiple Sclerosis, Myelin water imaging, water content

We established a new in-vivo measurement of the myelin water gap that can serve as a biomarker for myelination packing. In postmortem studies, it was shown that the water layer gap between healthy myelin membranes is compact. However, it changes during the demyelination and remyelination processes in MS patients. We developed a biophysical model based on the water fraction and multi-compartment T2 to estimate the water gap. Next, we designed a lipid phantom system with varying water gaps and validated it using Cryo-TEM. Our model successfully estimates the water gap in-vitro and shows a reliable estimation for in-vivo healthy volunteers.

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Bastien Herlin^1,2,3, Ivy Uszynski¹, Maëlig Chauvel¹, Cyril Poupon¹, and Sophie Dupont^2,3
1BAOBAB, NeuroSpin, Université Paris-Saclay, CNRS, CEA, Gif-sur-Yvette, France, ²AP-HP, Epilepsy Unit, GH Pitié-Salpêtrière-Charles Foix, Paris, France, ³Sorbonne Université, Paris, France

Keywords: White Matter, Brain

Optic radiations are tracts of importance for neurosurgery, especially their path within the temporal lobe. Using an advanced analysis pipeline relying on probabilistic tractography and fiber clustering, we processed the diffusion MRI data of the 1065 subjects of the HCP cohort and reconstructed a reference optic radiation bundle. From it, we subsequently extracted the optic radiations of each subject to study the variability of their morphometry. We identified a higher variability of their rostral extent, with a significant left-right difference (median distance to the temporal pole +/- standard deviation: left: 28.8 +/- 2.3 mm, right: 29.2 +/- 2.1 mm, p=1.10^-8).

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Emily Louise Baadsvik¹, Markus Weiger¹, Romain Froidevaux¹, Christoph Michael Schildknecht¹, Benjamin Victor Ineichen², and Klaas Paul Pruessmann^1
1Institute for Biomedical Engineering, ETH Zurich and University of Zurich, Zurich, Switzerland, ²Department of Neuroradiology, Clinical Neuroscience Center, University Hospital Zurich, University of Zurich, Zurich, Switzerland

Keywords: White Matter, Multiple Sclerosis, Myelin imaging

Direct access to myelin content through the detection of signals from the myelin lipid-protein bilayer can be achieved using advanced short-T₂ techniques. Here, we translate an existing procedure for mapping the myelin bilayer ex vivo to in vivo human application. Myelin maps are generated by fitting a three-component complex model to multi-TE (20–800µs) data acquired using the HYFI variant of the zero-TE sequence. The presented myelin maps exhibit expected white/grey matter contrast and are of reasonable quality. The step to in vivo represents an important advancement for myelin bilayer mapping as a promising emerging technique.

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Chenyang Li^1,2, Els Fieremans¹, Dmitry S. Novikov³, and Jiangyang Zhang^1
1Department of Radiology, NYU Grossman School of Medicine, New York, NY, United States, ²Vilcek Institute of Graduate Biomedical Sciences, NYU Grossman School of Medicine, New York, NY, United States, ³NYU Grossman School of Medicine, New York, NY, United States

Keywords: White Matter, Contrast Mechanisms, Water exchange

In white matter, myelin forms a barrier for water exchange between the intra-axonal and extra-axonal compartments. Although myelin is not directly visible in conventional diffusion MRI (dMRI), it may affect dMRI measurements via exchange. In this study, we compared two ways to combine magnetization transfer (MT) preparation with constant gradient dMRI (cg-dMRI) to study the effects of myelin on water exchange rate. Our results demonstrate that MT preparation can modulate the sensitivity of cg-dMRI to exchange by suppressing signals from a portion of exchanging spins and that placing MT preparation is more effective before diffusion encoding than during diffusion encoding.

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Mauro Zucchelli¹, Christos Papageorgakis¹, and Stefano Casagranda^1
1Department of R&D Advanced Applications, Olea Medical, La Ciotat, France

Keywords: White Matter, Diffusion Tensor Imaging, Denoising, CASA

Noise is a crucial problem that affects even the most advanced MRI techniques based on model fitting. It is therefore important to act on the raw data to remove as much noise as possible, while preserving the anatomical structures. Many techniques based on Principal Component Analysis (PCA) take advantage of the redundancy of information contained in multiphase data, to perform robust denoising. In this work, we introduce a new denoising method based on PC images. We show the added value of our technique on both the raw data and the derived fractional anisotropy map.

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Sharon Zlotzover¹, Noam Omer¹, Neta Stern¹, Dvir Radunsky¹, Tamar Blumenfeld-Katzir¹, and Noam Ben-Eliezer^1,2,3
1The Department of Biomedical Engineering, Tel-Aviv University, Tel-Aviv, Israel, ²Sagol School of Neuroscience, Tel-Aviv University, Tel Aviv, Israel, ³Center for Advanced Imaging Innovation and Research (CAI2R), New-York University Langone Medical Center, New York, NY, United States

Keywords: White Matter, Multiple Sclerosis, Myelin

Multicomponent (MC) T₂ analysis is a common technique for probing sub-voxel compartmentation in myelinated tissues. However, the task of resolving the T₂ spectra from a single voxel is ill-posed and highly sensitive to noise. Applying a spatially-global MC analysis of the tissue prior to the voxel-wise analysis promotes more stable solutions. Specifically, this approach identifies a specific set of MC T₂ features which are then used for fitting the signal in each voxel. Preliminary results suggest that the new data-driven approach can accurately estimate myelin content and correctly estimate myelin content in healthy tissue and in multiple sclerosis lesions.

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Noa van der Knaap^1,2,3, Simona Klinkhammer^1,4, Alida A. Postma^1,3, Arjen J.C. Slooter^5,6, Janneke Horn^7,8, Caroline M. van Heugten^4,9, Paulien H.M. Voorter^1,3, Merel M. van der Thiel^1,3, Gerhard S. Drenthen^1,3, Walter H. Backes^1,3, David E.J. Linden¹, Marcel J.H. Ariës^1,2, and Jacobus F.A. Jansen^1,3,10
1School for Mental Health & Neuroscience, Maastricht University, Maastricht, Netherlands, ²Department of Intensive Care, Maastricht University Medical Center, Maastricht, Netherlands, ³Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, Netherlands, ⁴Limburg Brain Injury Center, Maastricht University, Maastricht, Netherlands, ⁵Department of Intensive Care, University Medical Center Utrecht, Utrecht, Netherlands, ⁶UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, Netherlands, ⁷Department of Intensive Care, University Medical Center Amsterdam, Amsterdam, Netherlands, ⁸Amsterdam Neuroscience, University Medical Center Amsterdam, Amsterdam, Netherlands, ⁹Department of Neuropsychology and Psychopharmacology, Maastricht University, Maastricht, Netherlands, ¹⁰Department of Electrical Engineering, Eindhoven University of Technology, Eindhoven, Netherlands

Keywords: Infectious disease, COVID-19

Cerebral abnormalities are common in (severely affected) COVID-19 patients, although most reports only cover macrostructural abnormalities. Zooming in on microstructural abnormalities may better explain persisting COVID-19-related symptoms in COVID-19 survivors. Using intravoxel incoherent motion (IVIM) imaging, this study explored potential differences in microstructural and microvascular diffusivity between COVID-19 patients. No differences were found between patients admitted to the intensive care unit (ICU) (n=40) and general ward (n=38). However, increased disease severity in COVID-19 ICU patients was found to be associated with increased interstitial fluid content in the normal appearing white matter.