Siawoosh Mohammadi¹, Daniel Carey², Fred Dick³, Joern Diedrichsen⁴, Martina F. Callaghan⁵, Marty Sereno², Marco Reisert⁶, and Nikolaus Weiskopf^5
1Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Hamburg, Hamburg, Germany, ²Birkbeck/UCL Centre for NeuroImaging, London, London, United Kingdom, ³Birkbeck/UCL Centre for NeuroImaging, London, United Kingdom, ⁴UCL Institute of Cognitive Neurology, London, United Kingdom,⁵Wellcome Trust Centre for Neuroimaging, UCL Institute of Neurology, London, United Kingdom, ⁶University of Freiburg Medical Center, Freiburg, Germany

Quantitative MRI aims to generate measures that are specific to particular aspects of tissue microstructure. The g-ratio, quantifying the ratio between the inner and outer diameters of a fibre, has been shown to be related to the conductance velocity and exhibit plasticity in functional stimulation experiments. Here we present in vivo g-ratio measures and population statistics from 19 volunteers. The g-ratio was calculated by combining magnetisation saturation maps and high angular resolution diffusion imaging (HARDI) data. The MRI-based in vivo g-ratio measures are in good agreement with histological findings and have the potential to become an important neuroimaging biomarker.

T. Duval¹, S. Lévy¹, N. Stikov^1,2, A. Mezer³, T. Witzel⁴, B. Keil⁴, V. Smith⁴, L. L. Wald⁴, E. Klawiter⁴, and J. Cohen-Adad^1,5
1Institute of Biomedical Engineering, Polytechnique Montréal, Montréal, Québec, Canada, ²Montreal Neuronal Institute, McGill University, Montréal, Québec, Canada,³Edmond and Lily Safra Center for Brain Sciences (ELSC), The Hebrew University, Jerusalem, Israel, ⁴A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, United States, ⁵Functional Neuroimaging Unit, CRIUGM, Université de Montréal, Montréal, Québec, Canada

The myelin g-ratio is the ratio of the inner to the outer diameter of the myelin sheath. As such, it provides a measure of the myelin thickness that complements axon morphology, with high specificity towards demyelination. We demonstrate for the first time in vivo mapping of myelin g-ratio in the human spinal cord using 300 mT/m gradient system. Average g-ratio was 0.74, which is consistent with the reported optimal g-ratio of 0.70 in from histology work. The proposed method is feasible in a clinically-acceptable time and could be useful for assessing demyelination in multiple sclerosis.

Yoonho Nam¹ and Jongho Lee^1
1Department of Electrical and Computer Engineering, Seoul National University, Seoul, Seoul, Korea

Recently, a few studies investigated the signal decay characteristics of multi-echo GRE data in white matter. They showed that the signal is composed of two or three components which have different decay rates and frequency offsets. Based on this finding, complex signal models were suggested and they generated more reliable myelin water images (MWI). However, the resulting myelin water fraction (MWF) maps still suffer from artifacts which may originate from physiological sources (e.g. respiration and cardiac). In this work, we explored the contribution of respiration- and cardiac-induced noises in GRE-MWI and proposed an approach to compensate for the noises.

Han Jang¹, Yoonho Nam¹, Yangsoo Ryu¹, and Jongho Lee^1
1Department of Electrical and Computer Engineering, Seoul National University, Seoul, Seoul, Korea

A new myelin water imaging (ViSTa) was compared with DTI and MT.

Tianyou Xu¹, Sean Foxley¹, Michiel Kleinnijenhuis¹, and Karla Miller^1
1Oxford Centre for Functional Magnetic Resonance Imaging of the Brain, University of Oxford, Oxford, Oxfordshire, United Kingdom

This work investigates the role that the geometry of myelin has on susceptibility driven frequency shifts in white matter. Packed axons, representative of axon bundles, capture important aspects of tissue microstructure. Here we demonstrate via simulation that axonal shape has a nontrivial effect on the underlying distribution of proton frequencies and on the free induction decay signal magnitude and phase. To bridge simulation with physical reality, we derive a structural template from electron microscopy in excised white matter, which is then used to forward calculate the frequency distribution and signal.

Jae-Woong Kim¹, Seung Hong Choi², and Sung-Hong Park^1
1Korea Advanced Institute of Science and Technology, Daejeon, Korea, ²Seoul National University, Seoul, Korea

As methods for imaging myelination, we investigated signal sources of MT asymmetry (MTA) and inhomogeneous MT (IHMT), both of which utilize asymmetric aspects of MT spectrum. The phantom study showed similar specificity of MTA and IHMT to myelination. Under the same average power and total saturation duration, however, IHMT was independent of asymmetric shift in saturation offset frequencies but dependent on duration of each saturation RF pulse, whereas MTA showed characteristics opposite to IHMT. Although both IHMT and MTA may be useful for myelin imaging, further studies are necessary to understand the signal sources and sensitivity/specificity of MTA and IHMT.

Thanh D Nguyen¹, Sneha Pandya¹, Pascal Spincemaille¹, Susan A Gauthier¹, and Yi Wang^1
1Weill Cornell Medical College, New York, NY, United States

The objective of this study is to develop a fast absolute myelin water quantification method which does not require the use of an external water standard. Results in 6 volunteers show excellent agreement with the conventional method with a whole brain scan time of 7 min at 1.5T.

Benjamin Tendler¹, Samuel Wharton¹, and Richard Bowtell^1
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

Frequency difference mapping (FDM) is a novel technique that takes advantage of the non-linear temporal evolution of the phase in gradient echo sequences to obtain images that carry information about white matter (WM) microstructure. In contrast to other phase-based approaches for probing WM properties such as QSM and STI, FDM can yield local contrast that is sensitive to microstructure without requiring sophisticated filtering of phase images. Here a straightforward implementation of FDM is presented. The application of this approach to the measurement of the variation of microstructure across the corpus callosum in a study of 10 subjects is also described.

Benjamin Tendler¹, Samuel Wharton¹, and Richard Bowtell^1
1Sir Peter Mansfield Imaging Centre, University of Nottingham, Nottingham, Nottinghamshire, United Kingdom

The evolution of the magnitude and phase of gradient echo (GE) signals is sensitive to white matter (WM) microstructure. This effect has been characterised by using a three-pool model of WM, comprised of axonal, myelin and external compartments. This work compares the magnitude and phase signals produced using triple-exponential and geometric single/multiple-fibre models, showing that the triple-exponential model can be improved in the static dephasing regime by adding in terms which approximately account for frequency variation in the myelin and external compartments. We also demonstrate the effects of including a range of fibre sizes and diffusion in a multiple-fibre model.

Riccardo Metere¹, Markus Morawski², Henrik Marschner¹, Carsten Jäger², Tobias Streubel¹, Stefan Geyer¹, Katja Reimann¹, Andreas Schäfer¹, and Harald E. Möller^1
1Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany, ²Paul-Flechsig-Institute for Brain Research, University of Leipzig, Leipzig, Germany

The tissue composition of the brain can be related to different contrast sources in quantitative MRI imaging. Particularly, myelin and iron are considered to be the major source of MRI contrast, with strong correlation to T₁ and T₂^*, respectively. However, other components, and particularly the relatively abundant extracellular matrix, may play a role in the generation of MRI contrast. In this work we present preliminary experiments showing a contrast change in quantitative relaxation maps of a brain tissue sample before and after the digestion of the extracellular matrix, thus supporting the hypothesis that this componet contributes to MRI contrast.

Pippa Storey¹, Sohae Chung¹, Noam Ben-Eliezer¹, Gregory Lemberskiy¹, Yvonne W. Lui¹, and Dmitry S. Novikov^1
1Radiology Department, New York University School of Medicine, New York, NY, United States

Diffusion imaging has long been the method of choice for probing tissue microstructure. We show that signatures of microstructure are also present in the signals from conventional gradient and spin echo sequences. Preliminary results from phantoms containing polystyrene beads of known diameter demonstrate that the logarithms of the signals from both multiple gradient echo and single spin echo sequences decrease nonlinearly with TE, in agreement with theory. Numerical fits provide estimates of bead diameter and magnetic susceptibility in rough agreement with expected values. This has implications for studies of tissue microstructure and for interpretation of gradient and spin echo signals.

Peter van Gelderen¹, Xu Jiang¹, and Jeff H Duyn^1
1AMRI, LFMI, NINDS, National Institutes of Health, Bethesda, MD, United States

In human brain, T1-contrast is strongly affected by bound protons in myelin, whose rapid T1-relaxation influences the more mobile water protons through magnetization transfer. MT also affects the apparent, instantaneous T1-relaxation in inversion recovery (IR) experiments due to magnetization differences between bound and mobile protons generated by the inversion pulse. The amplitude and timescale of this effect was investigated comparing the IR following inversions at different B1-levels, which differentially saturate the bound proton magnetization. The white-matter IR resembled a two- exponential decay, with the more rapid decay having a 90ms time constant and a B1-dependent amplitude ranging from 12-19%.

Hye-Young Heo¹, Yi Zhang¹, Jochen Keupp², Yansong Zhao³, Michael Schar¹, Dong-Hoon Lee¹, Peter C.M van Zijl^1,4, and Jinyuan Zhou^1,4
1Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, Maryland, United States, ²Philips Research, Hamburg, Germany, ³Philips Healthcare, Cleveland, Ohio, United States, ⁴F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, Maryland, United States

APT-weighted imaging is a novel chemical exchange saturation transfer (CEST)-based MRI modality that gives contrast due to endogenous cytosolic protein and peptide content, as well as tissue pH, in vivo. In this abstract, several APTw-MRI sequences that are feasible for clinical applications were compared on phantoms, healthy subjects, and a patient with glioblastoma. Time-interleaved pTX sequences, particularly using the TSE acquisition, can maximize SNRs and APT-MRI effects on clinical scanners by avoiding RF amplifier limitations to the saturation pulses.

Yee Kai Tee¹, George WJ Harston², Nicholas Blockley³, Robert Frost³, Thomas W Okell³, Sivarajan Thandeswaran², Fintan Sheerin⁴, Peter Jezzard³, James Kennedy², Stephen Payne⁵, and Michael Chappell^5
1Department of Mechatronics and BioMedical Engineering, Universiti Tunku Abdul Rahman, KL, KL, Malaysia, ²Acute Stroke Programme, Radcliffe Department of Medicine, Oxford University, Oxfordshire, United Kingdom, ³Oxford Centre of Functional MRI of the Brain, Nuffield Department of Clinical Neurosciences, Oxford University, Oxfordshire, United Kingdom, ⁴Department of Neuroradiology, Oxford University Hospitals NHS Trust, Oxfordshire, United Kingdom, ⁵Department of Engineering Science, Institute of Biomedical Engineering, Oxford University, Oxfordshire, United Kingdom

Chemical exchange saturation transfer (CEST) data in acute stroke patients (within 6 hours of onset) were acquired to compare nuclear Overhauser enhancement mediated CEST (NOE-CEST) with apparent diffusion coefficient (ADC) and pH-weighted imaging using amide proton transfer (APT). This work is the first demonstration of NOE-CEST in acute human stroke. NOE-CEST provides a unique contrast compared to ADC and pH-weighted imaging in tissue that progresses to infarction, suggesting that NOE-CEST may offer a new insight in acute stroke management.

Julien Flament^1,2, Charlotte Gary^2,3, James Koch^2,4, Fabien Pifferi⁵, Emmanuel Comoy⁶, Jean-Luc Picq⁷, Julien Valette^2,3, and Marc Dhenain^2,3
1INSERM US27, CRC-MIRCen, Fontenay-aux-Roses, France, ²CEA/DSV/I2BM/MIRCen, Fontenay-aux-Roses, France, ³CNRS URA 2210, Fontenay-aux-Roses, France,⁴Department of Psychology, University of Wisconsin, Oshkosh, WI, United States, ⁵CNRS-MNHN UMR 7179, Brunoy, France, ⁶CEA/DSV/iMETI/SEPIA, Fontenay-aux-Roses, France, ⁷EA 2027, Université Paris 8, Saint-Denis, France