Frequency drift in MR spectroscopy at 3T

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 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 < 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.publishedVersio

The Role of Attention in Somatosensory Processing: A Multi-trait, Multi-method Analysis

Sensory processing abnormalities in autism have largely been described by parent report. This study used a multi-method (parent-report and measurement), multi-trait (tactile sensitivity and attention) design to evaluate somatosensory processing in ASD. Results showed multiple significant within-method (e.g., parent report of different traits)/cross-trait (e.g., attention and tactile sensitivity) correlations, suggesting that parent-reported tactile sensory dysfunction and performance-based tactile sensitivity describe different behavioral phenomena. Additionally, both parent-reported tactile functioning and performance-based tactile sensitivity measures were significantly associated with measures of attention. Findings suggest that sensory (tactile) processing abnormalities in ASD are multifaceted, and may partially reflect a more global deficit in behavioral regulation (including attention). Challenges of relying solely on parent-report to describe sensory difficulties faced by children/families with ASD are also highlighted

Hypoxia alters posterior cingulate cortex metabolism during a memory task: a 1H fMRS study

Environmental hypoxia (fraction of inspired oxygen (F(I)O(2)) ~ 0.120) is known to trigger a global increase in cerebral blood flow (CBF). However, regionally, a heterogeneous response is reported, particularly within the posterior cingulate cortex (PCC) where decreased CBF is found after two hours of hypoxic exposure. Furthermore, hypoxia reverses task-evoked BOLD signals within the PCC, and other regions of the default mode network, suggesting a reversal of neurovascular coupling. An alternative explanation is that the neural architecture supporting cognitive tasks is reorganised. Therefore, to confirm if this previous result is neural or vascular in origin, a measure of neural activity that is not haemodynamic-dependant is required. To achieve this, we utilised functional magnetic resonance spectroscopy to probe the glutamate response to memory recall in the PCC during normoxia (F(I)O(2) = 0.209) and after two hours of poikilocapnic hypoxia (F(I)O(2) = 0.120). We also acquired ASL-based measures of CBF to confirm previous findings of reduced CBF within the PCC in hypoxia. Consistent with previous findings, hypoxia induced a reduction in CBF within the PCC and other regions of the default mode network. Under normoxic conditions, memory recall was associated with an 8% increase in PCC glutamate compared to rest (P = 0.019); a change which was not observed during hypoxia. However, exploratory analysis of other neurometabolites showed that PCC glucose was reduced during hypoxia compared to normoxia both at rest (P = 0.039) and during the task (P = 0.046). We conclude that hypoxia alters the activity-induced increase in glutamate, which may reflect a reduction in oxidative metabolism within the PCC. The reduction in glucose in hypoxia reflects continued metabolism, presumably by non-oxidative means, without replacement of glucose due to reduced CBF

Investigation of anterior cingulate cortex gamma-aminobutyric acid and glutamate-glutamine levels in obsessive-compulsive disorder using magnetic resonance spectroscopy.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a relatively common and disabling psychiatric disorder whose pathophysiology is incompletely understood. In this study, we utilized magnetic resonance spectroscopy (MRS) in an effort to provide a better understanding of the role of brain gamma-aminobutyric acid (GABA) and glutamate in the pathophysiology of OCD. We hypothesized that beyond the separate effects of these neurotransmitter systems, a disruption in the balance between GABA and glutamate could be particularly relevant to OCD. METHODS: We obtained MRS measures of GABA and glutamate concentrations in the anterior cingulate cortex from 23 adult patients with OCD and 20 sex- and age-matched healthy community volunteers. Established clinical rating scales were used to assess the severities of OCD, anxiety, and depression symptoms. Statistical analysis involved the assessment of patient-control group differences in the individual measures of GABA and glutamate, as well as in the ratio of the GABA to glutamate measures. Additionally, we explored whether differences in the MRS measures existed between two subgroups of patients formed according to the severity of their OCD symptoms. Finally, we assessed the relations of demographic and clinical variables to the MRS measures. RESULTS: Patients with OCD displayed a higher estimated GABA level and a higher GABA to glutamate ratio than healthy participants, but no significant group differences were observed in the measure of glutamate. The MRS measures did not vary by subgroup and showed no correlations with demographic and clinical variables. CONCLUSIONS: These results indicate that GABA abnormalities within the anterior cingulate cortex contribute to the pathophysiology of OCD. The results fail to provide evidence that glutamate abnormalities alone are involved in adult OCD. Yet, it seems that a disruption in the balance between glutamate and GABA neurotransmission may have a particularly important role to play in OCD pathophysiology

Regionally specific human GABA concentration correlates with tactile discrimination thresholds

The neural mechanisms underlying variability in human sensory perception remain incompletely understood. In particular, few studies have attempted to investigate the relationship between in vivo measurements of neurochemistry and individuals' behavioral performance. Our previous work found a relationship between GABA concentration in the visual cortex and orientation discrimination thresholds (Edden et al., 2009). In the present study, we used magnetic resonance spectroscopy of GABA and psychophysical testing of vibrotactile frequency thresholds to investigate whether individual differences in tactile frequency discrimination performance are correlated with GABA concentration in sensorimotor cortex. Behaviorally, individuals showed a wide range of discrimination thresholds ranging from 3 to 7.6 Hz around the 25 Hz standard. These frequency discrimination thresholds were significantly correlated with GABA concentration (r = −0.58; p < 0.05) in individuals' sensorimotor cortex, but not with GABA concentration in an occipital control region (r = −0.04). These results demonstrate a link between GABA concentration and frequency discrimination in vivo, and support the hypothesis that GABAergic mechanisms have an important role to play in sensory discrimination

GABA levels in left and right sensorimotor cortex correlate across individuals

Differences in -aminobutyric acid (GABA) levels measured with Magnetic Resonance Spectroscopy have been shown to correlate with behavioral performance over a number of tasks and cortical regions. These correlations appear to be regionally and functionally specific. In this study, we test the hypothesis that GABA levels will be correlated within individuals for functionally related regions—the left and right sensorimotor cortex. In addition, we investigate whether this is driven by bulk tissue composition. GABA measurements using edited MRS data were acquired from the left and right sensorimotor cortex in 24 participants. T1-weighted MR images were also acquired and segmented to determine the tissue composition of the voxel. GABA level is shown to correlate significantly between the left and right regions (r = 0.64, p < 0.03). Tissue composition is highly correlated between sides, but does not explain significant variance in the bilateral correlation. In conclusion, individual differences in GABA level, which have previously been described as functionally and regionally specific, are correlated between homologous sensorimotor regions. This correlation is not driven by bulk differences in voxel tissue composition

A vibrotactile behavioral battery for investigating somatosensory processing in children and adults

The cortical dynamics of somatosensory processing can be investigated using vibrotactile psychophysics. It has been suggested that different vibrotactile paradigms target different cortical mechanisms, and a number of recent studies have established links between somatosensory cortical function and measurable aspects of behavior. The relationship between cortical mechanisms and sensory function is particularly relevant with respect to developmental disorders in which altered inhibitory processing has been postulated, such as in ASD and ADHD. In this study, a vibrotactile battery consisting of nine tasks (incorporating reaction time, detection threshold, and amplitude- and frequency discrimination) was applied to a cohort of healthy adults and a cohort of typically developing children to assess the feasibility of such a vibrotactile battery in both cohorts, and the performance between children and adults was compared. These results showed that children and adults were both able to perform these tasks with a similar performance, although the children were slightly less sensitive in frequency discrimination. Performance within different task-groups clustered together in adults, providing further evidence that these tasks tap into different cortical mechanisms, which is also discussed. This clustering was not observed in children, which may be potentially indicative of development and a greater variability. In conclusion, in this study, we showed that both children and adults were able to perform an extensive vibrotactile battery, and we showed the feasibility of applying this battery to other (e.g., neurodevelopmental) cohorts to probe different cortical mechanisms

Orientation discrimination performance is predicted by GABA concentration and gamma oscillation frequency in human primary visual cortex

Neuronal orientation selectivity has been shown in animal models to require corticocortical network cooperation and to be dependent on the presence of GABAergic inhibition. However, it is not known whether variability in these fundamental neurophysiological parameters leads to variability in behavioral performance. Here, using a combination of magnetic resonance spectroscopy, magnetoencephalography, and visual psychophysics, we show that individual performance on a visual orientation discrimination task is correlated with both the resting concentration of GABA and the frequency of stimulus-induced gamma oscillations in human visual cortex. Behaviorally, a strong oblique effect was found, with the mean angular threshold for oblique discrimination being five times higher than that for vertically oriented stimuli. Similarly, we found an oblique effect for the dependency of performance on neurophysiological parameters. Orientation detection thresholds were significantly negatively correlated with visual cortex GABA concentration for obliquely oriented patterns (r = −0.65, p < 0.015) but did not reach significance for vertically oriented stimuli (r = −0.39, p = 0.2). Similarly, thresholds for obliquely oriented stimuli were negatively correlated with gamma oscillation frequency (r = −0.65, p < 0.017), but thresholds for vertical orientations were not (r = −0.02, p = 0.9). Gamma oscillation frequency was positively correlated with GABA concentration in primary visual cortex (r = 0.67, p < 0.013). These results confirm the importance of GABAergic inhibition in orientation selectivity and demonstrate, for the first time, that interindividual performance on a simple visual task is linked to neurotransmitter concentration. The results also suggest a key role for GABAergic gamma oscillations in visual discrimination tasks

The Acquisition of Human B Cell Memory in Response to Plasmodium Falciparum Malaria

Immunity to Plasmodium falciparum (Pf), the most deadly agent of malaria, is only acquired after years of repeated infections and appears to wane rapidly without ongoing exposure. Antibodies (Abs) are central to malaria immunity, yet little is known about the B‐cell biology that underlies Pf‐specific humoral immunity. To address this gap in our knowledge we carried out a year‐long prospective study of the acquisition and maintenance of long‐lived plasma cells (LLPCs) and memory B cells (MBCs) in 225 individuals aged two to twenty‐five years in Mali, in an area of intense seasonal transmission. Using protein microarrays containing approximately 25% of the Pf proteome we determined that Pf‐specific Abs were acquired only gradually, in a stepwise fashion over years of Pf exposure. Pf‐specific Ab levels were significantly boosted each year during the transmission season but the majority of these Abs were short lived and were lost over the subsequent six month period of no transmission. Thus, we observed only a small incremental increase in stable Ab levels each year, presumably reflecting the slow acquisition LLPCs. The acquisition Pf‐specific MBCs mirrored the slow step‐wise acquisition of LLPCs. This slow acquisition of Pf‐specific LLPCs and MBCs was in sharp contrast to that of tetanus toxoid (TT)‐specific LLPCs and MBCs that were vi vi rapidly acquired and stably maintained following a single vaccination in individuals in this cohort. In addition to the development of normal MBCs we observed an expansion of atypical MBCs that are phenotypically similar to hyporesponsive FCRL4+ cells described in HIV‐infected individuals. Atypical MBC expansion correlated with cumulative exposure to Pf, and with persistent asymptomatic Pf‐infection in children, suggesting that the parasite may play a role in driving the expansion of atypical MBCs. Collectively, these observations provide a rare glimpse into the process of the acquisition of human B cell memory in response to infection and provide evidence for a selective deficit in the generation of Pf‐specific LLPCs and MBCs during malaria. Future studies will address the mechanisms underlying the slow acquisition of LLPCs and MBCs and the generation and function of atypical MBCs

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