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Background: The use of advanced magnetic resonance imaging (MRI) techniques in MS research has led to new insights in lesion evolution and disease outcomes. It has not yet been determined if, or how, pre-lesional abnormalities in normal-appearing white matter (NAWM) relate to the long-term evolution of new lesions. Objective: To investigate the relationship between abnormalities in MRI measures of axonal and myelin volume fractions (AVF and MVF) in NAWM preceding development of black-hole (BH) and non-BH lesions in people with MS. Methods: We obtained magnetization transfer and diffusion MRI at 6-month intervals in patients with MS to estimate MVF and AVF during lesion evolution. Lesions were classified as either BH or non-BH on the final imaging visit using T1 maps. Results: Longitudinal data from 97 new T2 lesions from 9 participants were analyzed; 25 lesions in 8 participants were classified as BH 6–12 months after initial appearance. Pre-lesion MVF, AVF, and MVF/AVF were significantly lower, and T1 was significantly higher, in the lesions that later became BHs ( p 0.05). Conclusion: The present work demonstrated that pre-lesion abnormalities are associated with worse long-term lesion-level outcome.

Resting-state fMRI studies have become very important in cognitive neuroscience because they are able to identify BOLD fluctuations in brain circuits involved in motor, cognitive, or perceptual processes without the use of an explicit task. Such approaches have been fruitful when applied to various disordered populations, or to children or the elderly. However, insufficient attention has been paid to the consequences of the loud acoustic scanner noise associated with conventional fMRI acquisition, which could be an important confounding factor affecting auditory and/or cognitive networks in resting-state fMRI. Several approaches have been developed to mitigate the effects of acoustic noise on fMRI signals, including sparse sampling protocols and interleaved silent steady state (ISSS) acquisition methods, the latter being used only for task-based fMRI. Here, we developed an ISSS protocol for resting-state fMRI (rs-ISSS) consisting of rapid acquisition of a set of echo planar imaging volumes following each silent period, during which the steady state longitudinal magnetization was maintained with a train of relatively silent slice-selective excitation pulses. We evaluated the test-retest reliability of intensity and spatial extent of connectivity networks of fMRI BOLD signal across three different days for rs-ISSS and compared it with a standard resting-state fMRI (rs-STD). We also compared the strength and distribution of connectivity networks between rs-ISSS and rs-STD. We found that both rs-ISSS and rs-STD showed high reproducibility of fMRI signal across days. In addition, rs-ISSS showed a more robust pattern of functional connectivity within the somatosensory and motor networks, as well as an auditory network compared with rs-STD. An increased connectivity between the default mode network and the language network and with the anterior cingulate cortex (ACC) network was also found for rs-ISSS compared with rs-STD. Finally, region of interest analysis showed higher interhemispheric connectivity in Heschl's gyri in rs-ISSS compared with rs-STD, with lower variability across days. The present findings suggest that rs-ISSS may be advantageous for detecting network connectivity in a less noisy environment, and that resting-state studies carried out with standard scanning protocols should consider the potential effects of loud noise on the measured networks.

Quantitative T2 data from an NIH-sponsored multi-center study of Normal Brain Development was used to perform automatic voxel-wise analysis of the changes in T2 evolution in the brain in healthy children within the age range from birth to 5 years. All data were non-linearly registered into a common coordinate space. The T2 parameters were estimated by 2 point fitting from the PD-weighted and T2-weighted image data, or by least-squares fitting of 4 data points when addition intermediate weighting images were available. The main result of this study is voxel-level map of monoexponential evolution of T2 in this age range indicating the delay (in months) and the rate (in 1/months) of development. The automatic maps are compared to manual region-of-interest based estimates of T2 evolution.

The fiber g-ratio is the ratio of the inner to the outer diameter of the myelin sheath of a myelinated axon. It has a limited dynamic range in healthy white matter, as it is optimized for speed of signal conduction, cellular energetics, and spatial constraints. In vivo imaging of the g-ratio in health and disease would greatly increase our knowledge of the nervous system and our ability to diagnose, monitor, and treat disease. MRI based g-ratio imaging was first conceived in 2011, and expanded to be feasible in full brain with preliminary results in 2013. This manuscript reviews the growing g-ratio imaging literature and speculates on future applications. It details the methodology for imaging the g-ratio with MRI, and describes the known pitfalls and challenges in doing so., This is the accepted version, accepted by NeuroImage. It contains minor revisions suggested by reviewers

Background Arterial spin labeling (ASL) perfusion-weighted imaging (PWI) by magnetic resonance imaging (MRI) has been shown to be useful for identifying asphyxiated newborns at risk of developing brain injury, whether or not therapeutic hypothermia was administered. However, this technique has been only rarely used in newborns until now, because of the challenges to obtain sufficient signal-to-noise ratio (SNR) and spatial resolution in newborns. Objective To compare two methods of ASL-PWI (i.e., single inversion-time pulsed arterial spin labeling [single TI PASL], and pseudo-continuous arterial spin labeling [pCASL]) to assess brain perfusion in asphyxiated newborns treated with therapeutic hypothermia and in healthy newborns. Design/methods We conducted a prospective cohort study of term asphyxiated newborns meeting the criteria for therapeutic hypothermia; four additional healthy term newborns were also included as controls. Each of the enrolled newborns was scanned at least once during the first month of life. Each MRI scan included conventional anatomical imaging, as well as PASL and pCASL PWI-MRI. Control and labeled images were registered separately to reduce the effect of motion artifacts. For each scan, the axial slice at the level of the basal ganglia was used for comparisons. Each scan was scored for its image quality. Quantification of whole-slice cerebral blood flow (CBF) was done afterwards using previously described formulas. Results A total number of 61 concomitant PASL and pCASL scans were obtained in nineteen asphyxiated newborns treated with therapeutic hypothermia and four healthy newborns. After discarding the scans with very poor image quality, 75% (46/61) remained for comparison between the two ASL methods. pCASL images presented a significantly superior image quality score compared to PASL images (p, Graphical abstract, Highlights • Two methods of ASL-PWI were compared in newborns, i.e. PASL and pCASL. • Both methods are feasible to assess brain perfusion in newborns. • pCASL is a better choice over PASL in newborns. • pCASL perfusion maps had a superior image quality.

Data sharing is becoming more of a requirement as technologies mature and as global research and communications diversify. As a result, researchers are looking for practical solutions, not only to enhance scientific collaborations, but also to acquire larger amounts of data, and to access specialized datasets. In many cases, the realities of data acquisition present a significant burden, therefore gaining access to public datasets allows for more robust analyses and broadly enriched data exploration. To answer this demand, the Montreal Neurological Institute has announced its commitment to Open Science, harnessing the power of making both clinical and research data available to the world (Owens, 2016a,b). As such, the LORIS and CBRAIN (Das et al., 2016) platforms have been tasked with the technical challenges specific to the institutional-level implementation of open data sharing, including: Comprehensive linking of multimodal data (phenotypic, clinical, neuroimaging, biobanking, and genomics, etc.) Secure database encryption, specifically designed for institutional and multi-project data sharing, ensuring subject confidentiality (using multi-tiered identifiers). Querying capabilities with multiple levels of single study and institutional permissions, allowing public data sharing for all consented and de-identified subject data. Configurable pipelines and flags to facilitate acquisition and analysis, as well as access to High Performance Computing clusters for rapid data processing and sharing of software tools. Robust Workflows and Quality Control mechanisms ensuring transparency and consistency in best practices. Long term storage (and web access) of data, reducing loss of institutional data assets. Enhanced web-based visualization of imaging, genomic, and phenotypic data, allowing for real-time viewing and manipulation of data from anywhere in the world. Numerous modules for data filtering, summary statistics, and personalized and configurable dashboards. Implementing the vision of Open Science at the Montreal Neurological Institute will be a concerted undertaking that seeks to facilitate data sharing for the global research community. Our goal is to utilize the years of experience in multi-site collaborative research infrastructure to implement the technical requirements to achieve this level of public data sharing in a practical yet robust manner, in support of accelerating scientific discovery.

// Philip Wong 1 , Ilana R. Leppert 2 , David Roberge 1 , Karim Boudam 1 , Paul D. Brown 3 , Thierry Muanza 4 , G. Bruce Pike 2,5 , Jeffrey Chankowsky 6 and Catalin Mihalcioiu 7 1 Department of Radiation Oncology, Centre Hospitalier de L’Universite de Montreal, Montreal, Quebec, Canada 2 Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada 3 Department of Radiation Oncology, Division of Radiation Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, United States of America 4 Department of Oncology, Jewish General Hospital, Montreal, Quebec, Canada 5 Departments of Radiology and Clinical Neurosciences, Hotchkiss Brain Institute, University of Calgary, Alberta, Canada 6 Diagnostic Radiology, McGill University Health Center, Montreal, Quebec, Canada 7 Department of Oncology, McGill University Health Center, Montreal, Quebec, Canada Correspondence to: Philip Wong, email: // Keywords : MRI, biomarker, imaging, radiotherapy, memantine Received : May 09, 2016 Accepted : May 17, 2016 Published : May 28, 2016 Abstract Purpose: This pilot prospective study sought to determine whether dynamic contrast enhanced MRI (DCE-MRI) could be used as a clinical imaging biomarker of tissue toxicity from whole brain radiotherapy (WBRT). Method: 14 patients who received WBRT were imaged using dynamic contrast enhanced DCE-MRI prior to and at 8-weeks, 16-weeks and 24-weeks after the initiation of WBRT. Twelve of the patients were also enrolled in the RTOG 0614 trial, which randomized patients to the use of placebo or memantine. After the unblinding of the treatments received by RTOG 0614 patients, DCE-MRI measures of tumor tissue and normal appearing white matter (NAWM) vascular permeability (Initial Area Under the Curve (AUC) Blood Adjusted) was analyzed. Cognitive, quality-of-life (QOL) assessment and blood samples were collected according to the patient’s ability to tolerate the exams. Circulating endothelial cells (CEC) were measured using flow cytometry. Results: Following WBRT, there was an increasing trend in the vascular permeability of tumors ( p =0.09) and NAWM ( p =0.06) with time. Memantine significantly ( p =0.01) reduced NAWM AUC changes following radiotherapy. Patients on memantine retained (COWA p = 0.03) better cognitive functions than those on placebo. No association was observed between the level of CEC and DCE-MRI changes, time from radiotherapy or memantine use. Conclusions: DCE-MRI can detect vascular damage secondary to WBRT. Our data suggests that memantine reduces WBRT-induced brain vasculature damages.

Studies in chronic stroke patients suggest that diffusion tensor imaging (DTI) parameters of the pyramidal tract (PT) relate to residual motor function. We performed a prospective controlled study to evaluate if the DTI parameters tract volume (TV) and fractional anisotropy (FA) in patients with acute subcortical infarcts are correlated with permanent PT damage and clinical outcome after 6 months.We acquired DTI in 18 stroke patients with subcortical ischemic infarcts either affecting the PT (PT group, n = 12) or not (non-PT group, n = 6) and in 7 age- and risk factor-matched controls at median times of 12 and 180 days. The PT was isolated using tractography and tract volume ratios (R(TV)) and FA ratios (R(FA)) were calculated (affected tract/unaffected tract). Ratios were compared within and between groups at initial and follow-up time points, as well as in tract portions above and below the infarcts, and were correlated to Rivermead Motor Function Test (RMFT) scores.Mean R(FA) and R(TV) of the PT group were smaller than those of both non-PT and control groups initially and at follow-up (p0.01). Tract portions above the infarct had lower R(TV) than below (p0.05). There was no significant change in R(FA) and R(TV) over time for the whole tract or tract portions. R(FA) and R(TV) both were highly correlated with initial and follow-up RMFT scores.DTI parameters of PT integrity acquired within the first weeks after acute subcortical stroke measure permanent ischemic PT damage and are highly correlated with residual motor function in the acute and chronic stage.

Diffusion weighted imaging (DWI) is known to be prone to artifacts related to motion originating from subject movement, cardiac pulsation and breathing, but also to mechanical issues such as table vibrations. Given the necessity for rigorous quality control and motion correction, users are often left to use simple heuristics to select correction schemes, but do not fully understand the consequences of such choices on the final analysis, moreover being at risk to introduce confounding factors in population studies. This paper reports work in progress towards a comprehensive evaluation framework of HARDI motion correction to support selection of optimal methods to correct for even subtle motion. We make use of human brain HARDI data from a well controlled motion experiment to simulate various degrees of motion corruption. Choices for correction include exclusion or registration of motion corrupted directions, with different choices of interpolation. The comparative evaluation is based on studying effects of motion correction on three different metrics commonly used when using DWI data, including similarity of fiber orientation distribution functions (fODFs), global brain connectivity via Graph Diffusion Distance (GDD), and reproducibility of prominent and anatomically defined fiber tracts. Effects of various settings are systematically explored and illustrated, leading to the somewhat surprising conclusion that a best choice is the alignment and interpolation of all DWI directions, not only directions considered as corrupted.

Purpose: To design a more accurate and reproducible technique for the measurement of blood–brain barrier (BBB) permeability in gadolinium-enhancing multiple sclerosis (MS) lesions. Materials and Methods: Four MS patients were scanned using a new dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI) protocol based on an uninterrupted two-part acquisition consisting of an initial part at high temporal and low spatial resolutions and a second part at low temporal and high spatial resolutions. The method preserves both the high spatial resolution needed for the often small size of lesions and the high temporal resolution required during the first minute after injection to sufficiently sample the first-pass bolus. Simulations compared the performance of this new protocol with the conventional one at low temporal and high spatial resolutions throughout. Results: The BBB permeability estimates changed by up to 33% between the two protocols. The new protocol led to simulated error on Ktrans of 7%–10%, versus 7%–30% with the conventional protocol, and was more robust with respect to offsets between acquisition and injection start times, differences in shape of the first-pass peak, and permeability values. Conclusion: The dual-temporal resolution protocol produces improved BBB permeability estimates and provides a more complete view of active inflammatory MS lesion pathology. J. Magn. Reson. Imaging 2011;33:1291–1300. © 2011 Wiley-Liss, Inc.

To establish normal age-related changes in the magnetic resonance (MR) T(2) relaxation time constants of brain using data collected as part of the National Institutes of Health (NIH) MRI Study of Normal Brain Development.This multicenter study of normal brain and behavior development provides both longitudinal and cross-sectional data, and has enabled us to investigate T(2) evolution in several brain regions in healthy children within the age range of birth through 4 years 5 months. Due to the multicenter nature of the study and the extended period of data collection, periodically scanned inanimate and human phantoms were used to assess intra- and intersite variability.The main finding of this work, based on over 340 scans, is the identification and parameterization of the monoexponential evolution of T(2) from birth through 4 years 5 months of age in various brain structures.The exponentially decaying T(2) behavior is believed to reflect the rapid changes in water content as well as myelination during brain development. The data will become publicly available as part of a normative pediatric MRI and clinical/behavioral database, thereby providing a basis for comparison in studies assessing normal brain development, and studies of deviations due to various neurological, neuropsychiatric, and developmental disorders.

The myelination of white matter from birth through the first years of life has been studied qualitatively and it is well know the myelination occurs in a orderly and predictable manner, proceeding in a caudocranial direction, from deep to superficial and from posterior to anterior. Even if the myelination is a continuous process, it is useful to characterize myelination evolution in normal brain development in order to better study demyelinating diseases. The quantification of myelination has only been studied for neonates. The original contribution of this study is to develop a method to characterize and visualize the myelination pattern using MRI data from a group of normal subjects from birth to just over 4 years of age. The method includes brain extraction and tissue classification in addition to the analysis of T2 relaxation times to attempt to separate myelinated and unmyelinated white matter. The results agree previously published qualitative observations.

We provide a detailed morphometric analysis of eight transmission electron micrographs (TEMs) obtained from the corpus callosum of one cynomolgus macaque. The raw TEM images are included in the article, along with the distributions of the axon caliber and the myelin g-ratio in each image. The distributions are analyzed to determine the relationship between axon caliber and g-ratio, and compared against the aggregate metrics (myelin volume fraction, fiber volume fraction, and the aggregate g-ratio), as defined in the accompanying research article entitled ‘In vivo histology of the myelin g-ratio with magnetic resonance imaging’ (Stikov et al., NeuroImage, 2015).

Post-acquisition motion correction is widely performed in diffusion-weighted imaging (DWI) to guarantee voxel-wise correspondence between DWIs. Whereas this is primarily motivated to save as many scans as possible if corrupted by motion, users do not fully understand the consequences of different types of interpolation schemes on the final analysis. Nonetheless, interpolation might increase the partial volume effect while not preserving the volume of the diffusion profile, whereas excluding poor DWIs may affect the ability to resolve crossing fibers especially with small separation angles. In this paper, we investigate the effect of interpolating diffusion measurements as well as the elimination of bad directions on the reconstructed fiber orientation diffusion functions and on the estimated fiber orientations. We demonstrate such an effect on synthetic and real HARDI datasets. Our experiments demonstrate that the effect of interpolation is more significant with small fibers separation angles where the exclusion of motion-corrupted directions decreases the ability to resolve such crossing fibers.