Search

INTRODUCTION: Drug development for neurodegenerative diseases such as Friedreich's ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA. METHODS: 200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich's Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers. DISCUSSION: Prioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease tr

PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the f

Background and purposeDeletion and duplication of chromosome 16p11.2 (BP4-BP5) have been associated with developmental disorders such as autism spectrum disorders, and deletion subjects exhibit a large (20-ms) delay of the auditory evoked cortical response as measured by magnetoencephalography (M100 latency). The purpose of this study was to use a multimodal approach to test whether changes in white matter microstructure are associated with delayed M100 latency.Materials and methodsThirty pediatric deletion carriers, 9 duplication carriers, and 39 control children were studied with both magnetoencephalography and diffusion MR imaging. The M100 latency and auditory system DTI measures were compared between groups and tested for correlation.ResultsIn controls, white matter diffusivity significantly correlated with the speed of the M100 response. However, the relationship between structure and function appeared uncoupled in 16p11.2 copy number variation carriers. The alterations to auditory system white matter microstructure in the 16p11.2 deletion only partially accounted for the 20-ms M100 delay. Although both duplication and deletion groups exhibit abnormal white matter microstructure, only the deletion group has delayed M100 latency.ConclusionsThese results indicate that gene dosage impacts factors other than white matter microstructure, which modulate conduction velocity.

© 2015, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is mad

© 2015, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is mad

Latency of electric (e.g., PI and NI) and magnetic (e.g., M100) auditory evoked components depends on age in typically developing children, with longer latencies for younger (4-6 years) and shorter, adult-like latencies for older (14-16 years) children. Age-related changes in evoked components provide indirect measures of auditory system maturation and reflect changes that occur during development. We use magnetoencephalography (MEG) to investigate maturational changes in cortical auditory systems in left (LH) and right (RH) hemispheres in children with autism disorder (AD) and Controls. We recorded auditory evoked responses over left and right temporal lobes in 17 Control and 15 AD children in the age range 8-16 years and measured M100 latency as a function of age, subject group and hemisphere. Linear regression analyses of age and M100 latency provided an estimate of the rate of latency change (ms/year) by hemisphere and subject group. Controls: M100 latency for the group ranged from 100.8 to 166.1 ms and varied linearly in both hemispheres, decreasing at a rate of -4 ms/year (LH) and -4.5 ms/year (RH). AD: M100 latency ranged from 116.2 to 186.2 ins. Slopes of regression lines did not differ from zero in either LH or RH. M100 latency showed a tendency to vary with age in LH, decreasing at a rate of -4.6 ms/year. M100 latency in RH increased slightly (at a rate of 0.8 ms/year) with age. Results provide evidence for a differential auditory system development in AD children which may reflect abnormalities in cortical maturational processes in AD. (C) 2003 Elsevier B.V. All rights reserved.

Latency of electric (e.g., PI and NI) and magnetic (e.g., M100) auditory evoked components depends on age in typically developing children, with longer latencies for younger (4-6 years) and shorter, adult-like latencies for older (14-16 years) children. Age-related changes in evoked components provide indirect measures of auditory system maturation and reflect changes that occur during development. We use magnetoencephalography (MEG) to investigate maturational changes in cortical auditory systems in left (LH) and right (RH) hemispheres in children with autism disorder (AD) and Controls. We recorded auditory evoked responses over left and right temporal lobes in 17 Control and 15 AD children in the age range 8-16 years and measured M100 latency as a function of age, subject group and hemisphere. Linear regression analyses of age and M100 latency provided an estimate of the rate of latency change (ms/year) by hemisphere and subject group. Controls: M100 latency for the group ranged from 100.8 to 166.1 ms and varied linearly in both hemispheres, decreasing at a rate of -4 ms/year (LH) and -4.5 ms/year (RH). AD: M100 latency ranged from 116.2 to 186.2 ins. Slopes of regression lines did not differ from zero in either LH or RH. M100 latency showed a tendency to vary with age in LH, decreasing at a rate of -4.6 ms/year. M100 latency in RH increased slightly (at a rate of 0.8 ms/year) with age. Results provide evidence for a differential auditory system development in AD children which may reflect abnormalities in cortical maturational processes in AD. (C) 2003 Elsevier B.V. All rights reserved.