Multimodal MRI as a diagnostic biomarker for amyotrophic lateral sclerosis

Objective Reliable biomarkers for amyotrophic lateral sclerosis ( ALS ) are needed, given the clinical heterogeneity of the disease. Here, we provide proof‐of‐concept for using multimodal magnetic resonance imaging ( MRI ) as a diagnostic biomarker for ALS . Specifically, we evaluated the added diagnostic utility of proton magnetic resonance spectroscopy ( MRS ) to diffusion tensor imaging ( DTI ). Methods Twenty‐nine patients with ALS and 30 age‐ and gender‐matched healthy controls underwent brain MRI which used proton MRS including spectral editing techniques to measure γ‐aminobutyric acid ( GABA ) and DTI to measure fractional anisotropy of the corticospinal tract. Data were analyzed using logistic regression, t ‐tests, and generalized linear models with leave‐one‐out analysis to generate and compare the resulting receiver operating characteristic ( ROC ) curves. Results The diagnostic accuracy is significantly improved when the MRS data were combined with the DTI data as compared to the DTI data only (area under the ROC curves ( AUC ) = 0.93 vs. AUC  = 0.81; P  = 0.05). The combined MRS and DTI data resulted in sensitivity of 0.93, specificity of 0.85, positive likelihood ratio of 6.20, and negative likelihood ratio of 0.08 whereas the DTI data only resulted in sensitivity of 0.86, specificity of 0.70, positive likelihood ratio of 2.87, and negative likelihood ratio of 0.20. Interpretation Combining multiple advanced neuroimaging modalities significantly improves disease discrimination between ALS patients and healthy controls. These results provide an important step toward advancing a multimodal MRI approach along the diagnostic test development pathway for ALS.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106065/1/acn330.pd

More GABA, less distraction: a neurochemical predictor of motor decision speed

People vary markedly in the efficiency with which they can resolve competitive action decisions, even simple ones such as shifting gaze to one stimulus rather than another. We found that an individual's ability to rapidly resolve such competition is predicted by the concentration of GABA, the main inhibitory neurotransmitter, in a region of frontal cortex that is relevant for eye movements, but not in a control region (occipital cortex)

Implementation of 3 T Lactate-Edited 3D 1H MR Spectroscopic Imaging with Flyback Echo-Planar Readout for Gliomas Patients

The purpose of this study was to implement a new lactate-edited 3D 1H magnetic resonance spectroscopic imaging (MRSI) sequence at 3 T and demonstrate the feasibility of using this sequence for measuring lactate in patients with gliomas. A 3D PRESS MRSI sequence incorporating shortened, high bandwidth 180° pulses, new dual BASING lactate-editing pulses, high bandwidth very selective suppression (VSS) pulses and a flyback echo-planar readout was implemented at 3 T. Over-prescription factor of PRESS voxels was optimized using phantom to minimize chemical shift artifacts. The lactate-edited flyback sequence was compared with lactate-edited MRSI using conventional elliptical k-space sampling in a phantom and volunteers, and then applied to patients with gliomas. The results demonstrated the feasibility of detecting lactate within a short scan time of 9.5 min in both phantoms and patients. Over-prescription of voxels gave less chemical shift artifacts allowing detection of lactate on the majority of the selected volume. The normalized SNR of brain metabolites using the flyback encoding were comparable to the SNR of brain metabolites using conventional phase encoding MRSI. The specialized lactate-edited 3D MRSI sequence was able to detect lactate in brain tumor patients at 3 T. The implementation of this technique means that brain lactate can be evaluated in a routine clinical setting to study its potential as a marker for prognosis and response to therapy

Molecular psychiatry of zebrafish

Due to their well-characterized neural development and high genetic homology to mammals, zebrafish (Danio rerio) have emerged as a powerful model organism in the field of biological psychiatry. Here, we discuss the molecular psychiatry of zebrafish, and its implications for translational neuroscience research and modeling central nervous system (CNS) disorders. In particular, we outline recent genetic and technological developments allowing for in vivo examinations, high-throughput screening and whole-brain analyses in larval and adult zebrafish. We also summarize the application of these molecular techniques to the understanding of neuropsychiatric disease, outlining the potential of zebrafish for modeling complex brain disorders, including attention-deficit/hyperactivity disorder (ADHD), aggression, post-traumatic stress and substance abuse. Critically evaluating the advantages and limitations of larval and adult fish tests, we suggest that zebrafish models become a rapidly emerging new field in modern molecular psychiatry research

Oblique Orientation Discrimination Thresholds Are Superior in Those with a High Level of Autistic Traits

Enhanced low-level perception, although present in individuals with autism, is not seen in individuals with high, but non-clinical, levels of autistic traits (Brock et al.in Percept Lond 40(6):739. doi:10.​1068/​p6953, 2011). This is surprising, as many of the higher-level visual differences found in autism have been shown to correlate with autistic traits in non-clinical samples. Here we measure vertical–oblique and, more difficult, oblique–oblique orientation discrimination thresholds in a non-clinical sample. As predicted, oblique–oblique thresholds provided a more sensitive test of orientation discrimination, and were negatively related to autistic traits (N = 94, r = −.356, p < .0001). We conclude that individual differences in orientation discrimination and autistic traits are related, and suggest that both of these factors could be mediated by increased levels of the inhibitory neurotransmitter GABA

Frequency drift in MR spectroscopy at 3T

Purpose: Heating of gradient coils and passive shim components is a common cause of instability in the B-0 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 first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p &lt; 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI.Discussion: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.</p

Improved prospective frequency correction for macromolecule-suppressed GABA editing with metabolite cycling at 3T

Purpose: To combine metabolite cycling with J-difference editing (MC MEGA) to allow for prospective frequency correction at each transient without additional acquisitions and compare it to water-suppressed MEGA-PRESS (WS MEGA) editing with intermittent prospective frequency correction. Methods: Macromolecule-suppressed gamma aminobutyric acid (GABA)-edited experiments were performed in a phantom and in the occipital lobe (OCC) (n = 12) and medial prefrontal cortex (mPFC) (n = 8) of the human brain. Water frequency consistency and average offset over acquisition time were compared. GABA multiplet patterns, signal intensities, and choline subtraction artifacts were evaluated. In vivo GABA concentrations were compared and related to frequency offset in the OCC. Results: MC MEGA was more stable with 21% and 32% smaller water frequency SDs in the OCC and mPFC, respectively. MC MEGA also had 39% and 40% smaller average frequency offsets in the OCC and mPFC, respectively. Phantom GABA multiplet patterns and signal intensities were similar. In vivo GABA concentrations were smaller in MC MEGA than in WS MEGA, with median (interquartile range) of 2.52 (0.27) and 2.29 (0.19) institutional units (i.u.), respectively in the OCC scans without prior DTI, and 0.99 (0.3) and 1.72 (0.5), respectively in the mPFC. OCC WS MEGA GABA concentrations, but not MC MEGA GABA concentrations were moderately correlated with frequency offset. mPFC WS MEGA spectra contained significantly more subtraction artifacts than MC MEGA spectra. Conclusion: MC MEGA is feasible and allows for prospective frequency correction at every transient. MC MEGA GABA concentrations were not biased by frequency offsets and contained less subtraction artifacts compared to WS MEGA

Improved prospective frequency correction for macromolecule-suppressed GABA editing with metabolite cycling at 3T

Macromolecule-suppressed GABA-editing with symmetrical suppression is often preferred over conventional GABA-editing due to its greater specificity. However, this pulse sequence is more sensitive to magnetic field instabilities than conventional GABA-editing. This leads to macromolecule contamination in the edited GABA signal. Here, we combine metabolite cycling with J-difference (MC-MEGA) editing to allow for prospective volume-localized frequency correction at each repetition time without the acquisition of additional water reference transients. We show here that prospective MC-MEGA reduces B0 field instability relative to intermittent prospective frequency correction with water suppressed (WS) MEGA and reduces macromolecule contamination and subtraction artifacts