Fast 3D rosette spectroscopic imaging of neocortical abnormalities at 3 T: Assessment of spectral quality.

PURPOSE: To use a fast 3D rosette spectroscopic imaging acquisition to quantitatively evaluate how spectral quality influences detection of the endogenous variation of gray and white matter metabolite differences in controls, and demonstrate how rosette spectroscopic imaging can detect metabolic dysfunction in patients with neocortical abnormalities. METHODS: Data were acquired on a 3T MR scanner and 32-channel head coil, with rosette spectroscopic imaging covering a 4-cm slab of fronto-parietal-temporal lobes. The influence of acquisition parameters and filtering on spectral quality and sensitivity to tissue composition was assessed by LCModel analysis, the Cramer-Rao lower bound, and the standard errors from regression analyses. The optimized protocol was used to generate normative white and gray matter regressions and evaluate three patients with neocortical abnormalities. RESULTS: As a measure of the sensitivity to detect abnormalities, the standard errors of regression for Cr/NAA and Ch/NAA were significantly correlated with the Cramer-Rao lower bound values (R = 0.89 and 0.92, respectively, both with P < 0.001). The rosette acquisition with a duration of 9.6 min, produces a mean Cramer-Rao lower bound (%) over the entire slab of 4.6 ± 2.6 and 5.8 ± 2.3 for NAA and Cr, respectively. This enables a Cr/NAA standard error of 0.08 (i.e., detection sensitivity of 25% for a 50/50 mixed gray and white matter voxel). In healthy controls, the regression of Cr/NAA versus fraction gray matter in the cingulate differs from frontal and parietal regions. CONCLUSIONS: Fast rosette spectroscopic imaging acquisitions with regression analyses are able to identify metabolic differences across 4-cm slabs of the brain centrally and over the cortical periphery with high efficiency, generating results that are consistent with clinical findings. Magn Reson Med 79:2470-2480, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

In vivo brain rosette spectroscopic imaging (RSI) with LASER excitation, constant gradient strength readout, and automated LCModel quantification for all voxels.

PURPOSE: To optimize the Rosette trajectories for high-sensitivity in vivo brain spectroscopic imaging and reduced gradient demands. METHODS: Using LASER localization, a rosette based sampling scheme for in vivo brain spectroscopic imaging data on a 3 Tesla (T) system is described. The two-dimensional (2D) and 3D rosette spectroscopic imaging (RSI) data were acquired using 20 × 20 in-plane resolution (8 × 8 mm(2) ), and 1 (2D) -18 mm (1.1 cc) or 12 (3D) -8 mm partitions (0.5 cc voxels). The performance of the RSI acquisition was compared with a conventional spectroscopic imaging (SI) sequence using LASER localization and 2D or 3D elliptical phase encoding (ePE). Quantification of the entire RSI data set was performed using an LCModel based pipeline. RESULTS: The RSI acquisitions took 32 s for the 2D scan, and as short as 5 min for the 3D 20 × 20 × 12 scan, using a maximum gradient strength Gmax=5.8 mT/m and slew-rate Smax=45 mT/m/ms. The Bland-Altman agreement between RSI and ePE CSI, characterized by the 95% confidence interval for their difference (RSI-ePE), is within 13% of the mean (RSI+ePE)/2. Compared with the 3D ePE at the same nominal resolution, the effective RSI voxel size was three times smaller while the measured signal-to-noise ratio sensitivity, after normalization for differences in effective size, was 43% greater. CONCLUSION: 3D LASER-RSI is a fast, high-sensitivity spectroscopic imaging sequence, which can acquire medium-to-high resolution SI data in clinically acceptable scan times (5-10 min), with reduced stress on the gradient system. Magn Reson Med 76:380-390, 2016. © 2015 Wiley Periodicals, Inc.

Glutamate and GABA contributions to medial prefrontal cortical activity to emotion: implications for mood disorders.

The dorsomedial prefrontal cortex (MdPFC) and anterior cingulate cortices (ACC) play a critical role in implicit emotion regulation; however the understanding of the specific neurotransmitters that mediate such role is lacking. In this study, we examined relationships between MdPFC concentrations of two neurotransmitters, glutamate and γ-amino butyric acid (GABA), and BOLD activity in ACC during performance of an implicit facial emotion-processing task. Twenty healthy volunteers, aged 20-35 years, were scanned while performing an implicit facial emotion-processing task, whereby presented facial expressions changed from neutral to one of the four emotions: happy, anger, fear, or sad. Glutamate concentrations were measured before and after the emotion-processing task in right MdPFC using magnetic resonance spectroscopy (MRS). GABA concentrations were measured in bilateral MdPFC after the emotion-processing task. Multiple regression models were run to determine the relative contribution of glutamate and GABA concentration, age, and gender to BOLD signal in ACC to each of the four emotions. Multiple regression analyses revealed a significant negative correlation between MdPFC GABA concentration and BOLD signal in subgenual ACC (p<0.05, corrected) to sad versus shape contrast. For the anger versus shape contrast, there was a significant negative correlation between age and BOLD signal in pregenual ACC (p<0.05, corrected) and a positive correlation between MdPFC glutamate concentration (pre-task) and BOLD signal in pregenual ACC (p<0.05, corrected). Our findings are the first to provide insight into relationships between MdPFC neurotransmitter concentrations and ACC BOLD signal, and could further understanding of molecular mechanisms underlying emotion processing in healthy and mood-disordered individuals.

Functional anatomy of the masking level difference, an fMRI study.

INTRODUCTION: Masking level differences (MLDs) are differences in the hearing threshold for the detection of a signal presented in a noise background, where either the phase of the signal or noise is reversed between ears. We use N0/Nπ to denote noise presented in-phase/out-of-phase between ears and S0/Sπ to denote a 500 Hz sine wave signal as in/out-of-phase. Signal detection level for the noise/signal combinations N0Sπ and NπS0 is typically 10-20 dB better than for N0S0. All combinations have the same spectrum, level, and duration of both the signal and the noise. METHODS: Ten participants (5 female), age: 22-43, with N0Sπ-N0S0 MLDs greater than 10 dB, were imaged using a sparse BOLD fMRI sequence, with a 9 second gap (1 second quiet preceding stimuli). Band-pass (400-600 Hz) noise and an enveloped signal (.25 second tone burst, 50% duty-cycle) were used to create the stimuli. Brain maps of statistically significant regions were formed from a second-level analysis using SPM5. RESULTS: The contrast NπS0- N0Sπ had significant regions of activation in the right pulvinar, corpus callosum, and insula bilaterally. The left inferior frontal gyrus had significant activation for contrasts N0Sπ-N0S0 and NπS0-N0S0. The contrast N0S0-N0Sπ revealed a region in the right insula, and the contrast N0S0-NπS0 had a region of significance in the left insula. CONCLUSION: Our results extend the view that the thalamus acts as a gating mechanism to enable dichotic listening, and suggest that MLD processing is accomplished through thalamic communication with the insula, which communicate across the corpus callosum to either enhance or diminish the binaural signal (depending on the MLD condition). The audibility improvement of the signal with both MLD conditions is likely reflected by activation in the left inferior frontal gyrus, a late stage in the what/where model of auditory processing.

Abnormal subcortical deep-gray matter susceptibility-weighted imaging filtered phase measurements in patients with multiple sclerosis: a case-control study.

OBJECTIVE: To investigate abnormal phase on susceptibility-weighted imaging (SWI)-filtered phase images indicative of iron content, in subcortical deep-gray matter (SDGM) of multiple sclerosis (MS) patients and healthy controls (HC), and to explore its relationship with MRI outcomes. METHODS: 169 relapsing-remitting (RR) and 64 secondary-progressive (SP) MS patients, and 126 age- and sex-matched HC were imaged on a 3T scanner. Mean phase of the abnormal phase tissue (MP-APT), normal phase tissue volume (NPTV) and normalized volume were determined for total SDGM, caudate, putamen, globus pallidus, thalamus, pulvinar nucleus of thalamus (PVN), hippocampus, amygdala, nucleus accumbens, red nucleus and substantia nigra. 63 HC were used for establishment of normal reference phase values, while additional 63 HC were used for blinded comparisons with MS patients. RESULTS: Increased MP-APT, decreased normalized volume and decreased NPTV were detected in total SDGM, caudate, putamen, globus pallidus, thalamus and PVN in MS patients compared to HC (p<.0004). MS patients also showed decreased volume in hippocampus (<.0001) and decreased NPTV in the hippocampus, amygdala and accumbens (<.0004). SPMS patients had increased MP-APT, decreased volume and decreased NPTV in total SDGM, caudate and amygdala compared to RRMS (p<.005), while individual measure differences were also detected in putamen, thalamus, hippocampus and accumbens (p<.006). RRMS patients showed a significant relationship between increased MP-APT and increased lesion burden and more advanced brain atrophy (p<.004). CONCLUSIONS: Abnormal phase, indicative of higher iron content was significantly increased in MS patients compared to HC, and was related to more severe lesion burden and brain atrophy.

Decreased brain venous vasculature visibility on susceptibility-weighted imaging venography in patients with multiple sclerosis is related to chronic cerebrospinal venous insufficiency.

BACKGROUND: The potential pathogenesis between the presence and severity of chronic cerebrospinal venous insufficiency (CCSVI) and its relation to clinical and imaging outcomes in brain parenchyma of multiple sclerosis (MS) patients has not yet been elucidated. The aim of the study was to investigate the relationship between CCSVI, and altered brain parenchyma venous vasculature visibility (VVV) on susceptibility-weighted imaging (SWI) in patients with MS and in sex- and age-matched healthy controls (HC). METHODS: 59 MS patients, 41 relapsing-remitting and 18 secondary-progressive, and 33 HC were imaged on a 3T GE scanner using pre- and post-contrast SWI venography. The presence and severity of CCSVI was determined using extra-cranial and trans-cranial Doppler criteria. Apparent total venous volume (ATVV), venous intracranial fraction (VIF) and average distance-from-vein (DFV) were calculated for various vein mean diameter categories: < .3 mm, .3-.6 mm, .6-.9 mm and > .9 mm. RESULTS: CCSVI criteria were fulfilled in 79.7% of MS patients and 18.2% of HC (p < .0001). Patients with MS showed decreased overall ATVV, ATVV of veins with a diameter < .3 mm, and increased DFV compared to HC (all p < .0001). Subjects diagnosed with CCSVI had significantly increased DFV (p < .0001), decreased overall ATVV and ATVV of veins with a diameter < .3 mm (p < .003) compared to subjects without CCSVI. The severity of CCSVI was significantly related to decreased VVV in MS (p < .0001) on pre- and post-contrast SWI, but not in HC. CONCLUSIONS: MS patients with higher number of venous stenoses, indicative of CCSVI severity, showed significantly decreased venous vasculature in the brain parenchyma. The pathogenesis of these findings has to be further investigated, but they suggest that reduced metabolism and morphological changes of venous vasculature may be taking place in patients with MS.

Hypoperfusion of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report.

BACKGROUND: Several studies have reported hypoperfusion of the brain parenchyma in multiple sclerosis (MS) patients. We hypothesized a possible relationship between abnormal perfusion in MS and hampered venous outflow at the extracranial level, a condition possibly associated with MS and known as chronic cerebrospinal venous insufficiency (CCSVI). METHODS: We investigated the relationship between CCSVI and cerebral perfusion in 16 CCSVI MS patients and 8 age- and sex-matched healthy controls. Subjects were scanned in a 3-T scanner using dynamic susceptibility, contrast-enhanced, perfusion-weighted imaging. Cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were measured in the gray matter (GM), white matter (WM) and the subcortical GM (SGM). The severity of CCSVI was assessed according to the venous hemodynamic insufficiency severity score (VHISS) on the basis of the number of venous segments exhibiting flow abnormalities. RESULTS: There was a significant association between increased VHISS and decreased CBF in the majority of examined regions of the brain parenchyma in MS patients. The most robust correlations were observed for GM and WM (r = -0.70 to -0.71, P < 0.002 and P corrected = 0.022), and for the putamen, thalamus, pulvinar nucleus of thalamus, globus pallidus and hippocampus (r = -0.59 to -0.71, P < 0.01 and P corrected < 0.05). No results for correlation between VHISS and CBV or MTT survived multiple comparison correction. CONCLUSIONS: This pilot study is the first to report a significant relationship between the severity of CCSVI and hypoperfusion in the brain parenchyma. These preliminary findings should be confirmed in a larger cohort of MS patients to ensure that they generalize to the MS population as a whole. Reduced perfusion could contribute to the known mechanisms of virtual hypoxia in degenerated axons.

Use of MR venography for characterization of the extracranial venous system in patients with multiple sclerosis and healthy control subjects.

PURPOSE: To investigate the differences in the extracranial venous system in patients with multiple sclerosis (MS) and healthy control (HC) subjects by using magnetic resonance (MR) venography. MATERIALS AND METHODS: This HIPAA-compliant, prospective study was approved by the local institutional review board, and all participants gave informed consent. Fifty-seven patients, 41 (72%) with relapsing-remitting MS and 16 (28%) with secondary-progressive MS, and 21 HC subjects were imaged with a 3-T MR unit by using two-dimensional (2D) time-of-flight (TOF) and three-dimensional (3D) time-resolved imaging of contrast kinetics (TRICKS) sequences. In addition, six MS patients and six HC subjects underwent two sequential MR venographic examinations during 1 week to test image-reimage reproducibility. The morphologic features of internal jugular vein flow were classified as absent, pinpoint, flattened, crescentic, or ellipsoidal flow. Only absent and pinpoint flow were considered abnormal. The flow of the vertebral veins was classified as absent or present. The prominence of collateral neck veins and venous asymmetries between the left and right sides were assessed. Differences among groups were tested with a two-tailed Mann-Whitney two-sample rank-sum test. RESULTS: No significant differences in morphologic features of flow in the internal jugular veins and vertebral veins were found between MS patients and HC subjects in any of the examined MR venographic parameters. No differences in asymmetry or prominence were found between MS patients and HC subjects. There was modest agreement (κ = 0.67) between 2D TOF and 3D TRICKS sequences. Image-reimage reproducibility showed modest agreement (κ = 0.66) for 2D TOF and low agreement for 3D TRICKS (κ = 0.33). CONCLUSION: No significant differences in the extracranial venous systems between MS patients and HC subjects were detected by using MR venography. Standardized guidelines are needed to define parameters for the presence of venous anomalies.

Rosette spectroscopic imaging: optimal parameters for alias-free, high sensitivity spectroscopic imaging.

PURPOSE: To optimize the Rosette trajectories for fast, high sensitivity spectroscopic imaging experiments and to compare this acquisition technique with other chemical shift imaging (CSI) methods. MATERIALS AND METHODS: A framework for comparing the sensitivity of the Rosette Spectroscopic Imaging (RSI) acquisition to other spectroscopic imaging experiments is outlined. Accounting for hardware constraints, trajectory parameters that provide for optimal sampling and minimal artifact production are found. Along with an analytical expression for the number of excitations to be used in an RSI experiment that is provided, the theoretical precompensation weights used for optimal image reconstruction are derived. RESULTS: The spectral response function for RSI is shown to be approximately the same as the point spread function of standard Fourier reconstructions. While the signal-to-noise ratio (SNR) for an RSI experiment is reduced by the inherent nonuniform sampling of these trajectories, their circular k-space support and speed of spatial encoding leads to greater SNR efficiency and improvements in the total data acquisition time relative to the gold standard CSI approach with square k-space support and to similar efficiency to spiral CSI acquisitions. Numerical simulations and in vivo experimental data are presented to demonstrate the properties of this data acquisition technique. CONCLUSION: This work demonstrates the use of Rosette trajectories and how to achieve improved efficiency for these trajectories in a two-dimensional spectroscopic imaging experiment.