Hadamard Encoding Research Articles

A 3D fast MR elastography sequence with interleaved multislab acquisition and Hadamard encoding.

To enhance the functional capability of MRI, this study aims to develop a novel MR elastography (MRE) sequence that achieves rapid acquisition without distortion artifacts. A displacement-encoded stimulated echo (DENSE) with multiphase acquisition scheme was used to capture wave images. A center-out golden-angle stack-of-stars sampling pattern was introduced for improved SNR and data incoherence. A combination of Hadamard encoding and interleaved multislab acquisition schemes was used to increase the acquisition efficiency of MRE data with multiple directions and phase offsets. A generalized parallel-imaging and compressed-sensing method was further applied to accelerate the acquisition process. The imaging results of the proposed sequence were compared with those from six gradient echo (GRE)/EPI/DENSE-based MRE sequences via phantom and brain acquisitions. The proposed sequence achieved a 6-fold acceleration compared with GRE MRE. With the application of a conventional parallel-imaging and compressed-sensing algorithm, the scanning speed was further accelerated by 8-fold, matching the speed of EPI-based MRE. Phantom tests revealed small variances in stiffness measurements across the seven sequences (< 9.23%). The proposed sequence exhibited a higher contrast-to-noise ratio (1.38) than the two EPI-based sequences (0.61/0.76) and similar to GRE-based sequences (1.34/1.22/1.58). Brain imaging validated the effectiveness of the proposed sequence in accurate stiffness estimation and distortion artifact avoidance. A rapid DENSE-based MRE sequence with interleaved multislab acquisition and Hadamard encoding was developed at a speed matching EPI-based sequences, without compromising SNR or introducing distortion artifacts.

Solid state NMR spectral editing of histidine, arginine and lysine using Hadamard encoding.

The NMR signals from protein sidechains are rich in information about intra- and inter-molecular interactions, but their detection can be complicated due to spectral overlap as well as conformational and hydrogen exchange. In this work, we demonstrate a protocol for multi-dimensional solid-state NMR spectral editing of signals from basic sidechains based on Hadamard matrix encoding. The Hadamard method acquires multi-dimensional experiments in such a way that both the backbone and under-sampled sidechain signals can be decoded for unambiguous editing in the 15 N spectral frequency dimension. All multi-dimensional 15 N-edited solid-state NMR experiments can be acquired using this strategy, thereby accelerating the acquisition of spectra spanning broad frequency bandwidth. Application of these methods to the ferritin nanocage, reveals signals from N atoms from His, Arg, Lys and Trp sidechains, as well as their tightly bound, ordered water molecules. The Hadamard approach adds to the arsenal of spectroscopic approaches for protein NMR signal detection.

Identification of neurotransmitter imbalances in the cingulate cortex of NMOSD patients using magnetic resonance spectroscopy.

Cognitive impairment affects 29-67% of patients with neuromyelitis optica spectrum disorder. Previous studies have reported glutamate homeostasis disruptions in astrocytes, leading to imbalances in gamma-aminobutyric acid levels. However, the association between these neurotransmitter changes and cognitive deficits remains inadequately elucidated. Point RESolved Spectroscopy and Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy techniques were utilized to evaluate gamma-aminobutyric acid, glutamate, glutathione levels, and excitation/inhibition balance in the anterior cingulate cortex, posterior cingulate cortex, and occipital cortex of 39 neuromyelitis optica spectrum disorder patients and 41 healthy controls. Cognitive function was assessed using neurocognitive scales. Results showed decreased gamma-aminobutyric acid levels alongside increased glutamate, glutathione, and excitation/inhibition ratio in the anterior cingulate cortex and posterior cingulate cortex of neuromyelitis optica spectrum disorder patients. Specifically, within the posterior cingulate cortex of neuromyelitis optica spectrum disorder patients, decreased gamma-aminobutyric acid levels and increased excitation/inhibition ratio correlated significantly with anxiety scores, whereas glutathione levels predicted diminished executive function. The results suggest that neuromyelitis optica spectrum disorder patients exhibit dysregulation in the GABAergic and glutamatergic systems in their brains, where the excitation/inhibition imbalance potentially acts as a neuronal metabolic factor contributing to emotional disorders. Additionally, glutathione levels in the posterior cingulate cortex region may serve as predictors of cognitive decline, highlighting the potential benefits of reducing oxidative stress to safeguard cognitive function in neuromyelitis optica spectrum disorder patients.

Simultaneous Measurement of GABA, Glutathione, and Glutamate-Glutamine in the Thalamus using Edited MR Spectroscopy: Feasibility and Applications in Traumatic Brain Injury.

MR spectroscopy (MRS) is a noninvasive tool for evaluating biochemical alterations, such as glutamate (Glu)/gamma-aminobutyric acid (GABA) imbalance and depletion of antioxidative glutathione (GSH) after traumatic brain injury (TBI). Thalamus, a critical and vulnerable region post-TBI, is challenging for MRS acquisitions, necessitating optimization to simultaneously measure GABA/Glu and GSH. To assess the feasibility and optimize acquisition and processing approaches for simultaneously measuring GABA, Glx (Glu + glutamine (Gln)), and GSH in the thalamus, employing Hadamard encoding and reconstruction of MEscher-GArwood (MEGA)-edited spectroscopy (HERMES). Prospective. 28 control subjects (age: 35.9 ± 15.1 years), and 17 mild TBI (mTBI) patients (age: 32.4 ± 11.3 years). 3T/T1-weighted magnetization-prepared rapid gradient-echo (MP-RAGE), HERMES. We evaluated the impact of acquisition with spatial saturation bands and post-processing with spectral alignment on HERMES performance in the thalamus among controls. Within-subject variability was examined in five controls through repeated scans within a week. The HERMES spectra in the posterior cingulate cortex (PCC) of controls were used as a reference for assessing HERMES performance in a reliable target. Furthermore, we compared metabolite levels and fitting quality in the thalamus between mTBI patients and controls. Unpaired t-tests and within-subject coefficient-of-variation (CV). A P-value <0.05 was deemed significant. HERMES spectra, acquired with saturation bands and processed with spectral alignment, yielded reliable metabolite measurements in the thalamus. The mean within-subject CV for GABA, Glx, and GSH levels were 18%, 10%, and 16% in the thalamus (7%, 9%, and 16% in the PCC). GABA (3.20 ± 0.60 vs 2.51 ± 0.55, P < 0.01) and Glx (8.69 ± 1.23 vs 7.72 ± 1.19, P = 0.03) levels in the thalamus were significantly higher in mTBI patients than in controls, with GSH (1.27 ± 0.35 vs 1.22 ± 0.28, P = 0.65) levels showing no significant difference. Simultaneous measuring GABA/Glx and GSH using HERMES is feasible in the thalamus, providing valuable insight into TBI. 2 TECHNICAL EFFICACY: Stage 2.

Glutamate measurements using edited MRS.

To demonstrate J-difference coediting of glutamate using Hadamard encoding and reconstruction of Mescher-Garwood-edited spectroscopy (HERMES). Density-matrix simulations of HERMES (TE 80 ms) and 1D J-resolved (TE 31-229 ms) of glutamate (Glu), glutamine (Gln), γ-aminobutyric acid (GABA), and glutathione (GSH) were performed. HERMES comprised four sub-experiments with editing pulses applied as follows: (A) 1.9/4.56 ppm simultaneously (ONGABA /ONGSH ); (B) 1.9 ppm only (ONGABA /OFFGSH ); (C) 4.56 ppm only (OFFGABA /ONGSH ); and (D) 7.5 ppm (OFFGABA /OFFGSH ). Phantom HERMES and 1D J-resolved experiments of Glu were performed. Finally, in vivo HERMES (20-ms editing pulses) and 1D J-resolved (TE 31-229 ms) experiments were performed on 137 participants using 3 T MRI scanners. LCModel was used for quantification. HERMES simulation and phantom experiments show a Glu-edited signal at 2.34 ppm in the Hadamard sum combination A+B+C+D with no overlapping Gln signal. The J-resolved simulations and phantom experiments show substantial TE modulation of the Glu and Gln signals across the TEs, whose average yields a well-resolved Glu signal closely matching the Glu-edited signal from the HERMES sum spectrum. In vivo quantification of Glu show that the two methods are highly correlated (p < 0.001) with a bias of ∼10%, along with similar between-subject coefficients of variation (HERMES/TE-averaged: ∼7.3%/∼6.9%). Other Hadamard combinations produce the expected GABA-edited (A+B-C-D) or GSH-edited (A-B+C-D) signal. HERMES simulation and phantom experiments show the separation of Glu from Gln. In vivo HERMES experiments yield Glu (without Gln), GABA, and GSH in a single MRS scan.

Hadamard Encoding Based Frequent Itemset Mining under Local Differential Privacy

Hadamard Encoding Based Frequent Itemset Mining under Local Differential Privacy

Ongoing oxidative stress in individuals with post-acute sequelae of COVID-19.

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 infection is associated with lower plasma glutathione (GSH) levels due to oxidative stress. However, plasma levels may not reflect brain GSH levels. Individuals with post-acute sequelae of COVID-19 (PASC) have a higher prevalence of cognitive fatigue, which might be related to altered brain γ-aminobutyric-acid (GABA) levels. Hence, our study aims to measure the brain GSH and GABA levels in PASC. 29 PASC participants and 24 uninfected controls were recruited for this study. Each was evaluated with detailed neuropsychiatric assessments and an edited proton MRS (Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy, HERMES) method to measure GABA and GSH concentrations in predominantly grey matter (GM) and predominantly white matter (WM) brain frontal voxels. PASC participants were 219 ± 137 days since their COVID-19 diagnosis. Nine individuals with PASC were hospitalized. Compared to controls, individuals with PASC had similar levels of GABA in both brain regions, but lower GSH and greater age-related GSH decline in the frontal GM region. The lower-than-normal frontal GM GSH level in participants with PASC suggest that they have ongoing oxidative stress in the brain, and that older individuals may be even more vulnerable to oxidative stress.

Whole-brain mapping of mouse CSF flow via HEAP-METRIC phase-contrast MRI.

PurposeCSF plays important roles in clearing brain waste and homeostasis. However, mapping whole‐brain CSF flow in the rodents is difficult, primarily due to its assumed very low velocity. Therefore, we aimed to develop a novel phase‐contrast MRI method to map whole‐brain CSF flow in the mouse brain.MethodsA novel generalized Hadamard encoding–based multi‐band scheme (dubbed HEAP‐METRIC, Hadamard Encoding APproach of Multi‐band Excitation for short TR Imaging aCcelerating) using complex Hadamard matrix was developed and incorporated into conventional phase contrast (PC)‐MRI to significantly increase SNR.ResultsSlow flow phantom imaging validated HEAP‐METRIC PC‐MRI’s ability to achieve fast and accurate mapping of slow flow velocities (~102 µm/s). With the SNR gain afforded by HEAP‐METRIC scheme, high‐resolution (0.08 × 0.08 mm in‐plane resolution and 36 0.4 mm slices) PC‐MRI was completed in 21 min for whole‐brain CSF flow mapping in the mouse. Using this novel method, we provide the first report of whole‐brain CSF flow in the awake mouse brain with an average flow velocity of ~200 µm/s. Furthermore, HEAP‐METRIC PC‐MRI revealed CSF flow was reduced by isoflurane anesthesia, accompanied by reduction of glymphatic function as measured by dynamic contrast‐enhanced MRI.ConclusionWe developed and validated a generalized HEAP‐METRIC PC‐MRI for mapping low velocity flow. With this method, we have achieved the first whole‐brain mapping of awake mouse CSF flow and have further revealed that anesthesia reduces CSF flow velocity.

The Extended Hadamard Transform: Sensitivity-Enhanced NMR Experiments Among Labile and Non-Labile 1 Hs of SARS-CoV-2-derived RNAs.

Hadamard encoded saturation transfer can significantly improve the efficiency of NOE‐based NMR correlations from labile protons in proteins, glycans and RNAs, increasing the sensitivity of cross‐peaks by an order of magnitude and shortening experimental times by ≥100‐fold. These schemes, however, fail when tackling correlations within a pool of labile protons – for instance imino‐imino correlations in RNAs or amide‐amide correlations in proteins. Here we analyze the origin of the artifacts appearing in these experiments and propose a way to obtain artifact‐free correlations both within the labile pool as well as between labile and non‐labile 1Hs, while still enjoying the gains arising from Hadamard encoding and solvent repolarizations. The principles required for implementing what we define as the extended Hadamard scheme are derived, and its clean, artifact‐free, sensitivity‐enhancing performance is demonstrated on RNA fragments derived from the SARS‐CoV‐2 genome. Sensitivity gains per unit time approaching an order of magnitude are then achieved in both imino‐imino and imino‐amino/aromatic protons 2D correlations; similar artifact‐free sensitivity gains can be observed when carrying out extended Hadamard encodings of 3D NOESY/HSQC‐type experiments. The resulting spectra reveal significantly more correlations than their conventionally acquired counterparts, which can support the spectral assignment and secondary structure determination of structured RNA elements.

Glutamate, GABA and glutathione in adults with persistent post-concussive symptoms

Persistent post-concussive symptoms (PPCS) are debilitating and endure beyond the usual recovery period after mild traumatic brain injury (mTBI). Altered neurotransmission, impaired energy metabolism and oxidative stress have been examined acutely post-injury but have not been explored extensively in those with persistent symptoms. Specifically, the antioxidant glutathione (GSH) and the excitatory and inhibitory metabolites, glutamate (Glu) and γ-aminobutyric acid (GABA), are seldom studied together in the clinical mTBI literature. While Glu can be measured using conventional magnetic resonance spectroscopy (MRS) methods at 3 Tesla, GABA and GSH require the use of advanced MRS methods. Here, we used the recently established Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) to simultaneously measure GSH and GABA and short-echo time point resolved spectroscopy (PRESS) to measure Glu to gain new insight into the pathophysiology of PPCS. Twenty-nine adults with PPCS (mean age: 45.69 years, s.d.: 10.73, 22 females, 7 males) and 29 age- and sex-matched controls (mean age: 43.69 years, s.d.: 11.00) completed magnetic resonance spectroscopy scans with voxels placed in the anterior cingulate and right sensorimotor cortex. Relative to controls, anterior cingulate Glu was significantly reduced in PPCS. Higher anterior cingulate GABA was significantly associated with a higher number of lifetime mTBIs, suggesting GABA may be upregulated with repeated incidence of mTBI. Furthermore, GSH in both regions of interest was positively associated with symptoms of sleepiness and headache burden. Collectively, our findings suggest that the antioxidant defense system is active in participants with PPCS, however this may be at the expense of other glutamatergic functions such as cortical excitation and energy metabolism.

Hadamard-encoded dual-voxel SPECIAL: Short-TE MRS acquired in two brain regions simultaneously using Hadamard encoding.

The spin-echo, full-intensity acquired localized (SPECIAL) sequence is a method for single-voxel, localized MRS in vivo with short TEs. In this study we modified the SPECIAL sequence to simultaneously record spectra from two volumes of interest. This new technique is called Hadamard-encoded dual-voxel SPECIAL (HD-SPECIAL). The SPECIAL sequence consists of a spin echo localized to a column of tissue, preceded by a slice-selective inversion pulse in alternating scans to invert a section of the column. Full localization is achieved by subtraction of the inversion-on scans from the inversion-off scans. In HD-SPECIAL, the two-step inversion scheme is replaced by a four-step Hadamard-encoded scheme involving single-band and dual-band inversion pulses to select two regions of the spin-echo column. By appropriate Hadamard combination of the four acquired shots, spectra can be reconstructed from both desired regions. This approach does not rely on parallel imaging reconstruction. Using a 3T scanner, HD-SPECIAL localization is demonstrated both in phantoms and in the human brain in vivo, and the performance of HD-SPECIAL is assessed by comparing with the conventional SPECIAL sequence. Phantom and in vivo measurements show excellent agreement between measures from HD-SPECIAL and SPECIAL sequences. Relative to consecutive SPECIAL measurements from two regions, HD-SPECIAL reduces the total scan time 2-fold with minimal penalty in terms of spectral quality or SNR. The HD-SPECIAL sequence enables reliable acquisition of MR spectra simultaneously from two regions at 3 T, offering the potential to study interregional variations in metabolite concentrations.

Reliability and Reproducibility of Hadamard Encoded Pseudo-Continuous Arterial Spin Labeling in Healthy Elderly.

The perfusion parameters cerebral blood flow (CBF) and arterial transit time (ATT) measured with arterial spin labeling (ASL) magnetic resonance imaging (MRI) provide valuable essentials to assess the integrity of cerebral tissue. Brain perfusion changes, due to aging, an intervention, or neurodegenerative diseases for example, could be investigated in longitudinal ASL studies with reliable ASL sequences. Generally, pseudo-continuous ASL (pCASL) is preferred because of its larger signal-to-noise ratio (SNR) compared to pulsed ASL (PASL) techniques. Available pCASL versions differ regarding their feature details. To date only little is known about the reliability and reproducibility of CBF and ATT measures obtained with the innovative Hadamard encoded pCASL variant, especially if applied on participants in old age. Therefore, we investigated an in-house developed Hadamard encoded pCASL sequence on a group of healthy elderly at two different 3 Tesla Siemens MRI systems (Skyra and mMR Biograph) and evaluated CBF and ATT reliability and reproducibility for several regions-of-interests (ROI). Calculated within-subject coefficients of variation (wsCV) demonstrated an excellent reliability of perfusion measures, whereas ATT appeared to be even more reliable than CBF [e.g., wsCV(CBF) = 2.9% vs. wsCV(ATT) = 2.3% for a gray matter (GM) ROI on Skyra system]. Additionally, a substantial agreement of perfusion values acquired on both MRI systems with an inter-session interval of 78 ± 17.6 days was shown by high corresponding intra-class correlation (ICC) coefficients [e.g., ICC(CBF) = 0.704 and ICC(ATT) = 0.754 for a GM ROI]. The usability of this novel Hadamard encoded pCASL sequence might improve future follow-up perfusion studies of the aging and/or diseased brain.

Diagnostic Accuracy of Screening Arterial Spin-Labeling MRI Using Hadamard Encoding for the Detection of Reduced CBF in Adult Patients with Ischemic Moyamoya Disease.

Adult patients with ischemic Moyamoya disease are advised to undergo selective revascularization surgery based on cerebral hemodynamics. The purpose of this study was to determine the diagnostic accuracy of arterial spin-labeling MR imaging using Hadamard-encoded multiple postlabeling delays for the detection of reduced CBF in such patients. Thirty-seven patients underwent brain perfusion SPECT and pseudocontinuous arterial spin-labeling MR imaging using standard postlabeling delay (1525 ms) and Hadamard-encoded multiple postlabeling delays. For Hadamard-encoded multiple postlabeling delays, based on data obtained from the 7 sub-boluses with combinations of different labeling durations and postlabeling delays, CBF corrected by the arterial transit time was calculated on a voxel-by-voxel basis. Using a 3D stereotaxic template, we automatically placed ROIs in the ipsilateral cerebellar hemisphere and 5 MCA territories in the symptomatic cerebral hemisphere; then, the ratio of the MCA to cerebellar ROI was calculated. The area under the receiver operating characteristic curve for detecting reduced SPECT-CBF ratios (<0.686) was significantly greater for the Hadamard-encoded multiple postlabeling delays-CBF ratios (0.885) than for the standard postlabeling delay-CBF ratios (0.786) (P = .001). The sensitivity and negative predictive value for the Hadamard-encoded multiple postlabeling delays-CBF ratios were 100% (95% confidence interval, 100%-100%) and significantly higher than the sensitivity (95% CI, 44%-80%) and negative predictive value (95% CI, 88%-97%) for the standard postlabeling delay-CBF ratio, respectively. ASL MR imaging using Hadamard-encoded multiple postlabeling delays may be applicable as a screening tool because it can detect reduced CBF on brain perfusion SPECT with 100% sensitivity and a 100% negative predictive value in adult patients with ischemic Moyamoya disease.

A New 3-D Imaging Technique Integrating Ultrafast Compounding, Hadamard Encoding, and Reconfigurable Fresnel Lensing

Crossed electrode arrays address some of the challenges associated with 3-D ultrasound imaging because of the significant reduction in the number of elements ( 2N versus N2 ). However, creating a two-way focused 3-D image in real time is difficult with these arrays because azimuth and elevation dimensions cannot be beamformed at the same time. This work describes a new 3-D imaging technique that uses the flexibility of bias-sensitive substrates to create a high-quality elevation focus on a crossed electrode array. The principle behind this technique is to perform conventional compound imaging with an azimuth set of electrodes while implementing a bias controllable elevation lens with an elevation set of electrodes. On transmit, the biases are chosen to mimic a Fresnel lens. Then, on receive, the Hadamard coding is implemented along the elevation dimension. After decoding, we gain the RF data for each element across the elevation aperture even though there is effectively only one channel in that dimension. A 30-MHz, 128-element crossed electrode relaxor array was fabricated on a 1-3 electrostrictive composite substrate and was used to demonstrate the performance of the imaging technique. The on-axis -6-dB beamwidths were simulated to be 175 and [Formula: see text] in the azimuth and elevation directions, respectively, and the focus remained isotropic in the furthest elevation slice. Images were generated of a wire phantom to confirm the performance of the azimuth and elevational radiation patterns with good agreement between simulation and experiment. High-resolution 3-D volumetric images were generated of an ex vivo rat brain. Images of the cerebellum showed that the white and gray matter tracts could clearly be visualized with isometric resolution in both the azimuth and elevation dimensions.

Focal corticarl dysplasia in epilepsy is associated with GABA increase

PurposeFocal cortical dysplasia (FCD) is a major cause of drug-resistant epilepsy; however the underlying epileptogenic mechanisms of FCD metabolism in epilepsy patients remain unclear. The aim of this study is to detect alterations of γ-aminobutyric acid (GABA), glutathione (GSH), and the composite of glutamate and glutamine (Glx) in MRI-typical and neuropathologically confirmed FCD-associated epilepsy using Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES). Materials and methodsFourteen epileptic patients suspected to be caused by FCD and 14 healthy controls were enrolled prospectively in this study; all subjects underwent a 3 T MRI scan, including 3D T1 weighted imaging and HERMES. The GABA signal detected by HERMES also contains signals from macromolecules and homocarnosine, so it is referred as GABA+. Signals of GABA+, GSH and Glx detected by HERMES from tumor foci, contralateral cerebral regions, and healthy controls were quantified using Gannet. Fitting errors and signal to noise ratios (SNRs) of GABA + signals were also recorded. Differences of GABA+, GSH, Glx, fitting error and SNR of GABA + among three groups were analyzed using linear mixed effects models. ResultsTwelve FCD-associated epilepsy patients (7 females, aged 21.9 ± 9.3 years) and 12 matched healthy controls (7 females, aged 22.8 ± 9.8 years) were finally enrolled in this study. ANOVA results indicated that GABA levels were significantly increased in FCD foci compared with contralateral regions (p = 0.008) and with healthy controls (p = 0.003), while no difference was found in GSH and Glx levels. No difference of fitting errors or SNR of GABA + was found among FCD foci, contralateral regions and healthy controls. ConclusionsIncreased GABA levels were found in FCD foci that indicated GABA may play a central role in the pathophysiology of FCD patients with epilepsy.

GSH and GABA decreases in IDH1-mutated low-grade gliomas detected by HERMES spectral editing at 3 T in vivo

Isocitrate dehydrogenase 1 (IDH1) mutational status is an important prognostic biomarker in gliomas. γ-aminobutyric acid (GABA) and reduced glutathione (GSH) play an important role in energy production, which is related to tumor progression. Hadamard Encoding and Reconstruction of Mega-Edited Spectroscopy (HERMES) is able to detect GABA and GSH in healthy controls. This study aims to examine GABA and GSH alterations in IDH1-mutated low-grade gliomas using HERMES. We prospectively enrolled 14 suspected low-grade gliomas and 6 healthy control patients in this study, all cases underwent a 3 T MRI scan, including T1-weighted imaging and HERMES acquisition with a volume of interest 3 × 3 × 3 cm3. HERMES detects a “GABA+” signal that includes contributions from macromolecules and homocarnosine. GABA+ and GSH in tumor foci (group 1), contralateral cerebral regions (group 2) and healthy controls (group 3) were quantified using Gannet. The fitting errors and SNR of HERMES for GABA+ and GSH were analyzed; FWHM of the unsuppressed water signal was also recorded. The Wilcoxon signed-rank test was performed to test for differences between contralateral GABA+ and GSH levels, and differences in GABA+, GSH and fitting errors/SNR between the three groups were analyzed using analysis of variance (ANOVA). Eleven IDH1-mutant low-grade gliomas (5 Female and 6 Male, age 33–69) and 6 healthy subjects (2 Female and 4 Male, age 35–60) were finally enrolled this study. The mean water linewidth across all subjects was 9.67 ± 2.28 Hz. The Wilcoxon signed-rank test revealed that GABA+ and GSH were decreased significantly in glioma foci compared with contralateral regions, whereas no differences were seen between the left and right regions in healthy controls. ANOVA showed that GABA+ and GSH levels in tumor were lower than contralaterally and in healthy controls, while no differences were observed between the contralateral healthy tissue and healthy controls. No differences of fitting errors or SNR were found between tumors, contralateral regions or healthy controls. Our results suggest that HERMES is a reliable tool to simultaneously measure GABA and GSH alterations in low-grade gliomas with IDH1 mutations.

Sensitive and simplified: a combinatorial acquisition of five distinct 2D constant-time 13C-1H NMR protein correlation spectra.

A procedure is presented for the substantial simplification of 2D constant-time 13C-1H heteronuclear single-quantum correlation (HSQC) spectra of 13C-enriched proteins. In this approach, a single pulse sequence simultaneously records eight sub-spectra wherein the phases of the NMR signals depend on spin topology. Signals from different chemical groups are then stratified into different sub-spectra through linear combination based on Hadamard encoding of 13CHn multiplicity (n = 1, 2, and 3) and the chemical nature of neighboring 13C nuclei (aliphatic, carbonyl/carboxyl, aromatic). This results in five sets of 2D NMR spectra containing mutually exclusive signals from: (i) 13Cβ-1Hβ correlations of asparagine and aspartic acid, 13Cγ-1Hγ correlations of glutamine and glutamic acid, and 13Cα-1Hα correlations of glycine, (ii) 13Cα-1Hα correlations of all residues but glycine, and (iii) 13Cβ-1Hβ correlations of phenylalanine, tyrosine, histidine, and tryptophan, and the remaining (iv) aliphatic 13CH2 and (v) aliphatic 13CH/13CH3 resonances. As HSQC is a common element of many NMR experiments, the spectral simplification proposed in this article can be straightforwardly implemented in experiments for resonance assignment and structure determination and should be of widespread utility.

An MRI-based switched gradient impulse response characterization method with uniform eigenmode excitation

Switching gradients generate eddy currents and mechanical vibrations of the gradient assembly causing errors in the gradient time integrals. This results in image distortions in k-space and inaccuracies in q-space imaging. The purpose of this work is to develop an MRI based unbiased measurement of the switched gradient impulse response function (sGIRF). A new gradient pattern, called the Tukey windowed Shifted Sine-Integral (Tw-SSI) pulse, is introduced to excite the gradient eigenmodes uniformly over a user-defined bandwidth. A 3D MRI-based method with Hadamard encoding was developed to map the spatiotemporal magnetic field generated after the excitation pulse to obtain the sGIRF for all the three gradient axes simultaneously. Compared to an energy-equivalent traditional trapezoidal pulse, the Tw-SSI pulse is able to excite the weak bandlimited cross-terms of the sGIRF by uniformly distributing the energy across eigenmodes. The developed field mapping method is sensitive enough to capture both the direct and cross-terms in the sGIRF. The various mechanical resonant modes of the gradient coils are also revealed, which were found to last longer than eddy currents in the shielded gradient coil studied. Tunable Tw-SSI pulse offers the flexibility to perform unbiased sGIRF measurements over a bandwidth of interest. Rapid MRI field mapping can be easily implemented in any MRI system. The method may be used to perform gradient pre-emphasis, to evaluate new gradient coil designs, and to characterize higher order shims.

Hadamard acquisition of 13 C-13 C 2-D correlation NMR spectra.

We show that a multiselective excitation with Hadamard encoding is a powerful tool for 2-D acquisition of 13 C─13 C homonuclear correlations. This method is not designed to improve the sensitivity, but rather to reduce the experiment time, provided there is sufficient sensitivity. Therefore, it allows fast acquisition of such 2-D spectra in labeled molecules. The technique has been demonstrated using a U─13 C─15 N histidine hydrochloride monohydrate sample allowing each point of the build-up curves of the 13 C─13 C cross-peaks to be recorded within 4 min 35 s, which is very difficult with conventional methods. Using the U─13 C─15 N f-MLF sample, we have demonstrated that the method can be applied to molecules with 14 13 C resonances with a minimum frequency separation of 240 Hz.

An evaluation of the reproducibility of 1H-MRS GABA and GSH levels acquired in healthy volunteers with J-difference editing sequences at varying echo times

Recent advances in J-difference-edited proton magnetic resonance spectroscopy (1H MRS) data acquisition and processing have led to the development of Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy (HERMES) techniques, which enable the simultaneous measurement of ɣ-aminobutyric acid (GABA), the primary inhibitory amino acid neurotransmitter in the central nervous system, and of glutathione (GSH), the most abundant antioxidant in living tissue, at the commonly available magnetic field strength of 3 T. However, the reproducibility of brain levels of GABA and GSH measured across multiple scans in human subjects using HERMES remains to be established. In the present study, twelve healthy volunteers completed two consecutive HERMES scans of the dorsal anterior cingulate cortex (dACC) to assess the test-retest reproducibility of the technique for GABA and GSH measurements at TE = 80 ms. Eleven of the twelve participants additionally completed two consecutive MEGA-PRESS scans at TE = 120 ms, with editing pulses configured for GSH acquisition, to compare the reliability of GSH in the same voxel measured using the standard MEGA-PRESS at TE = 120 ms. The primary findings of study were that, 1) the coefficient of variation (CV) of measuring GABA with HERMES was 16.7%, which is in agreement with the reliability we previously reported for measuring GABA using MEGA-PRESS; and 2) the reliability of measuring GSH with MEGA-PRESS at TE = 120 ms was more than twice as high as that for measuring the antioxidant with HERMES at TE = 80 ms (CV = 7.3% vs. 19.0% respectively). These findings suggest that HERMES and MEGA-PRESS offer similar reliabilities for measuring GABA, while MEGA-PRESS at TE = 120 ms is more reliable for measuring GSH relative to HERMES at TE = 80 ms.