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

PURPOSE: CSF 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. METHODS: A 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. RESULTS: Slow 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. CONCLUSION: We 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 1 Hs, 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.

In Vivo Brain Glutathione is Higher in Older Age and Correlates with Mobility.

Brain markers of oxidative damage increase with advancing age. In response, brain antioxidant levels may also increase with age, although this has not been well investigated. Here, we used edited magnetic resonance spectroscopy to quantify endogenous levels of glutathione (GSH, one of the most abundant brain antioxidants) in 37 young [mean: 21.8 (2.5) years; 19 female] and 23 older adults [mean: 72.8 (8.9) years; 19 female]. Accounting for age-related atrophy, we identified higher frontal and sensorimotor GSH levels for the older compared with the younger adults. For the older adults only, higher sensorimotor (but not frontal) GSH was correlated with poorer balance and gait. This suggests a regionally specific relationship between higher brain oxidative stress levels and motor performance declines with age. We suggest these findings reflect an upregulation of GSH in response to increasing brain oxidative stress with normal aging. Together, these results provide insight into age differences in brain antioxidant levels and implications for motor function.

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.

Accelerated spin-echo functional MRI using multisection excitation by simultaneous spin-echo interleaving (MESSI) with complex-encoded generalized slice dithered enhanced resolution (cgSlider) simultaneous multislice echo-planar imaging.

PURPOSE: Spin-echo functional MRI (SE-fMRI) has the potential to improve spatial specificity when compared with gradient-echo fMRI. However, high spatiotemporal resolution SE-fMRI with large slice-coverage is challenging as SE-fMRI requires a long echo time to generate blood oxygenation level-dependent (BOLD) contrast, leading to long repetition times. The aim of this work is to develop an acquisition method that enhances the slice-coverage of SE-fMRI at high spatiotemporal resolution. THEORY AND METHODS: An acquisition scheme was developed entitled multisection excitation by simultaneous spin-echo interleaving (MESSI) with complex-encoded generalized slice dithered enhanced resolution (cgSlider). MESSI uses the dead-time during the long echo time by interleaving the excitation and readout of 2 slices to enable 2× slice-acceleration, while cgSlider uses the stable temporal background phase in SE-fMRI to encode/decode 2 adjacent slices simultaneously with a "phase-constrained" reconstruction method. The proposed cgSlider-MESSI was also combined with simultaneous multislice (SMS) to achieve further slice-acceleration. This combined approach was used to achieve 1.5-mm isotropic whole-brain SE-fMRI with a temporal resolution of 1.5 s and was evaluated using sensory stimulation and breath-hold tasks at 3T. RESULTS: Compared with conventional SE-SMS, cgSlider-MESSI-SMS provides 4-fold increase in slice-coverage for the same repetition time, with comparable temporal signal-to-noise ratio. Corresponding fMRI activation from cgSlider-MESSI-SMS for both fMRI tasks were consistent with those from conventional SE-SMS. Overall, cgSlider-MESSI-SMS achieved a 32× encoding-acceleration by combining Rinplane × MB × cgSlider × MESSI = 4 × 2 × 2 × 2. CONCLUSION: High-quality, high-resolution whole-brain SE-fMRI was acquired at a short repetition time using cgSlider-MESSI-SMS. This method should be beneficial for high spatiotemporal resolution SE-fMRI studies requiring whole-brain coverage.

Robust arterial transit time and cerebral blood flow estimation using combined acquisition of Hadamard-encoded multi-delay and long-labeled long-delay pseudo-continuous arterial spin labeling: a simulation and in vivo study.

Arterial transit time (ATT) prolongation causes an error of cerebral blood flow (CBF) measurement during arterial spin labeling (ASL). To improve the accuracy of ATT and CBF in patients with prolonged ATT, we propose a robust ATT and CBF estimation method for clinical practice. The proposed method consists of a three-delay Hadamard-encoded pseudo-continuous ASL (H-pCASL) with an additional-encoding and single-delay with long-labeled long-delay (1dLLLD) acquisition. The additional-encoding allows for the reconstruction of a single-delay image with long-labeled short-delay (1dLLSD) in addition to the normal Hadamard sub-bolus images. Five different images (normal Hadamard 3 delay, 1dLLSD, 1dLLLD) were reconstructed to calculate ATT and CBF. A Monte Carlo simulation and an in vivo study were performed to access the accuracy of the proposed method in comparison to normal 7-delay (7d) H-pCASL with equally divided sub-bolus labeling duration (LD). The simulation showed that the accuracy of CBF is strongly affected by ATT. It was also demonstrated that underestimation of ATT and CBF by 7d H-pCASL was higher with longer ATT than with the proposed method. Consistent with the simulation, the 7d H-pCASL significantly underestimated the ATT compared to that of the proposed method. This underestimation was evident in the distal anterior cerebral artery (ACA; P = 0.0394) and the distal posterior cerebral artery (PCA; 2 P = 0.0255). Similar to the ATT, the CBF was underestimated with 7d H-pCASL in the distal ACA (P = 0.0099), distal middle cerebral artery (P = 0.0109), and distal PCA (P = 0.0319) compared to the proposed method. Improving the SNR of each delay image (even though the number of delays is small) is crucial for ATT estimation. This is opposed to acquiring many delays with short LD. The proposed method confers accurate ATT and CBF estimation within a practical acquisition time in a clinical setting.

Advanced Hadamard-encoded editing of seven low-concentration brain metabolites: Principles of HERCULES.

PURPOSE: To demonstrate the framework of a novel Hadamard-encoded spectral editing approach for simultaneously detecting multiple low-concentration brain metabolites in vivo at 3T. METHODS: HERCULES (Hadamard Editing Resolves Chemicals Using Linear-combination Estimation of Spectra) is a four-step Hadamard-encoded editing scheme. 20-ms editing pulses are applied at: (A) 4.58 and 1.9 ppm; (B) 4.18 and 1.9 ppm; (C) 4.58 ppm; and (D) 4.18 ppm. Edited signals from γ-aminobutyric acid (GABA), glutathione (GSH), ascorbate (Asc), N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), aspartate (Asp), lactate (Lac), and likely 2-hydroxyglutarate (2-HG) are separated with reduced signal overlap into distinct Hadamard combinations: (A+B+C+D); (A+B-C-D); and (A-B+C-D). HERCULES uses a novel multiplexed linear-combination modeling approach, fitting all three Hadamard combinations at the same time, maximizing the amount of information used for model parameter estimation, in order to quantify the levels of these compounds. Fitting also allows estimation of the levels of total choline (tCho), myo-inositol (Ins), glutamate (Glu), and glutamine (Gln). Quantitative HERCULES results were compared between two grey- and white-matter-rich brain regions (11 min acquisition time each) in 10 healthy volunteers. Coefficients of variation (CV) of quantified measurements from the HERCULES fitting approach were compared against those from a single-spectrum fitting approach, and against estimates from short-TE PRESS data. RESULTS: HERCULES successfully segregates overlapping resonances into separate Hadamard combinations, allowing for the estimation of levels of seven coupled metabolites that would usually require a single 11-min editing experiment each. Metabolite levels and CVs agree well with published values. CVs of quantified measurements from the multiplexed HERCULES fitting approach outperform single-spectrum fitting and short-TE PRESS for most of the edited metabolites, performing only slightly to moderately worse than the fitting method that gives the lowest CVs for tCho, NAA, NAAG, and Asp. CONCLUSION: HERCULES is a new experimental approach with the potential for simultaneous editing and multiplexed fitting of up to seven coupled low-concentration and six high-concentration metabolites within a single 11-min acquisition at 3T.

Ultra-high resolution brain metabolite mapping at 7 T by short-TR Hadamard-encoded FID-MRSI.

MRSI in the brain at ≥7 T is a technique of great promise, but has been limited mainly by low B0/B1+-homogeneity, specific absorption rate restrictions, long measurement times, and low spatial resolution. To overcome these limitations, we propose an ultra-high resolution (UHR) MRSI sequence that provides a 128×128 matrix with a nominal voxel volume of 1.7×1.7×8mm3 in a comparatively short measurement time. A clinically feasible scan time of 10-20min is reached via a short TR of 200 ms due to an optimised free induction decay-based acquisition with shortened water suppression as well as parallel imaging (PI) using Controlled Aliasing In Parallel Imaging Results IN Higher Acceleration (CAIPIRINHA). This approach is not limited to a rectangular region of interest in the centre of the brain, but also covers cortical brain regions. Transversal pulse-cascaded Hadamard encoding was able to further extend the coverage to 3D-UHR-MRSI of four slices (100×100×4 matrix size), with a measurement time of 17min. Lipid contamination was removed during post-processing using L2-regularisation. Simulations, phantom and volunteer measurements were performed. The obtained single-slice and 3D-metabolite maps show the brain in unprecedented detail (e.g., hemispheres, ventricles, gyri, and the contrast between grey and white matter). This facilitates the use of UHR-MRSI for clinical applications, such as measurements of the small structures and metabolic pathologic deviations found in small Multiple Sclerosis lesions.

Analysis and improvement of motion encoding in magnetic resonance elastography.

Magnetic resonance elastography (MRE) utilizes phase contrast magnetic resonance imaging (MRI), which is phase locked to externally generated mechanical vibrations, to measure the three-dimensional wave displacement field. At least four measurements with linear-independent encoding directions are necessary to correct for spurious phase contributions if effects from imaging gradients are non-negligible. In MRE, three encoding schemes have been used: unbalanced four- and six-point and balanced four-point ('tetrahedral') encoding. The first two sensitize to motion with orthogonal gradients, with the four-point method acquiring a single reference scan without motion sensitization, whereas three additional scans with inverted gradients are used with six-point encoding, leading to two-fold higher displacement-to-noise ratio (DNR) and 50% longer scan duration. Balanced four-point (tetrahedral) encoding encodes along the four diagonals of a cube, with one direction serving as a reference for the other three encoding directions, similar to four-point encoding. The objective of this work is to introduce a theoretical framework to compare different motion sensitization strategies with respect to their motion encoding efficiency in two fundamental encoding limits, the gradient strength limit and the dynamic range limit, which are both placed in relation to conventional gradient recalled echo (GRE)- and spin echo (SE)-based MRE sequences. We apply the framework to the three aforementioned schemes and show that the motion encoding efficiency of unbalanced four- and six-point encoding schemes in the gradient-limited regime can be increased by a factor of 1.5 when using all physical gradient channels concurrently. Furthermore, it is demonstrated that reversing the direction of the reference in balanced four-point (tetrahedral) encoding results in the Hadamard encoding scheme, which leads to increased DNR by 2 compared with balanced four-point encoding and 2.8 compared with unbalanced four-point encoding. As an example, we show that optimal encoding can be utilized to reduce the acquisition time of standard liver MRE in vivo from four to two breath holds.

Fast experiments for structure elucidation of small molecules: Hadamard NMR with multiple receivers.

We propose several significant improvements to the PANSY (Parallel NMR SpectroscopY) experiments-PANSY COSY and PANSY-TOCSY. The improved versions of these experiments provide sufficient spectral information for structure elucidation of small organic molecules from just two 2D experiments. The PANSY-TOCSY-Q experiment has been modified to allow for simultaneous acquisition of three different types of NMR spectra-1D C-13 of non-protonated carbon sites, 2D TOCSY and multiplicity edited 2D HETCOR. In addition the J-filtered 2D PANSY-gCOSY experiment records a 2D HH gCOSY spectrum in parallel with a (1) J-filtered HC long-range HETCOR spectrum as well as offers a simplified data processing. In addition to parallel acquisition, further time savings are feasible because of significantly smaller F1 spectral windows as compared to the indirect detection experiments. Use of cryoprobes and multiple receivers can significantly alleviate the sensitivity issues that are usually associated with the so called direct detection experiments. In cases where experiments are sampling limited rather than sensitivity limited further reduction of experiment time is achieved by using Hadamard encoding. In favorable cases the total recording time for the two PANSY experiments can be reduced to just 40 s. The proposed PANSY experiments provide sufficient information to allow the CMCse software package (Bruker) to solve structures of small organic molecules.

Three-dimensional Hadamard-encoded proton spectroscopic imaging in the human brain using time-cascaded pulses at 3 Tesla.

PURPOSE: To reduce the specific-absorption-rate (SAR) and chemical shift displacement (CSD) of three-dimensional (3D) Hadamard spectroscopic imaging (HSI) and maintain its point spread function (PSF) benefits. METHODS: A 3D hybrid of 2D longitudinal, 1D transverse HSI (L-HSI, T-HSI) sequence is introduced and demonstrated in a phantom and the human brain at 3 Tesla (T). Instead of superimposing each of the selective Hadamard radiofrequency (RF) pulses with its N single-slice components, they are cascaded in time, allowing N-fold stronger gradients, reducing the CSD. A spatially refocusing 180° RF pulse following the T-HSI encoding block provides variable, arbitrary echo time (TE) to eliminate undesirable short T2 species' signals, e.g., lipids. RESULTS: The sequence yields 10-15% better signal-to-noise ratio (SNR) and 8-16% less signal bleed than 3D chemical shift imaging of equal repetition time, spatial resolution and grid size. The 13 ± 6, 22 ± 7, 24 ± 8, and 31 ± 14 in vivo SNRs for myo-inositol, choline, creatine, and N-acetylaspartate were obtained in 21 min from 1 cm(3) voxels at TE ≈ 20 ms. Maximum CSD was 0.3 mm/ppm in each direction. CONCLUSION: The new hybrid HSI sequence offers a better localized PSF at reduced CSD and SAR at 3T. The short and variable TE permits acquisition of short T2 and J-coupled metabolites with higher SNR.

Hadamard slice encoding for reduced-FOV diffusion-weighted imaging.

PURPOSE: To improve the clinical utility of diffusion-weighted imaging (DWI) by extending the slice coverage of a high-resolution reduced field-of-view technique. THEORY: Challenges in achieving high spatial resolution restrict the use of DWI in assessment of small structures such as the spinal cord. A reduced field-of-view method with 2D echo-planar radiofrequency (RF) excitation was recently proposed for high-resolution DWI. Here, a Hadamard slice-encoding scheme is proposed to double the slice coverage by exploiting the periodicity of the 2D echo-planar RF excitation profile. METHODS: A 2D echo-planar RF pulse and matching multiband refocusing RF pulses were designed using the Shinnar-Le Roux algorithm to reduce band interference, and variable-rate selective excitation to shorten the pulse durations. Hadamard-encoded images were resolved through a phase-preserving image reconstruction. The performance of the method was evaluated via simulations, phantom experiments, and in vivo high-resolution axial DWI of spinal cord. RESULTS: The proposed scheme successfully extends the slice coverage, while preserving the sharp excitation profile and the reliable fat suppression of the original method. For in vivo axial DWI of the spinal cord, an in-plane resolution of 0.7 × 0.7 mm(2) was achieved with 16 slices. CONCLUSION: The proposed Hadamard slice-encoding scheme doubles the slice coverage of the 2D echo-planar RF reduced field-of-view method without any scan-time penalty.

Integrated Short-TE and Hadamard-edited Multi-Sequence (ISTHMUS) for Advanced MRS.

Background: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study. Methods: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions. After acquisition, ISTHMUS data were separated into the PRESS and HERCULES portions for analysis and modeled separately using Osprey. In vivo experiments were performed in 10 healthy volunteers (6 female; 29.5±6.6 years). Each volunteer underwent two scans on the same day. Differences in metabolite measurements were examined. T2 correction based on the dual-TE water integrals were compared with: 1) T2 correction based the default white matter and gray matter T2 reference values in Osprey; 2) shorter WM and GM T2 values from recent literature; and 3) reduced CSF fractions. Results: No significant difference in linewidth was observed between PRESS and HERCULES. Bilateral thalamus spectra had produced significantly higher (p<0.001) linewidth compared to the other three regions. Linewidth measurements were similar between scans, with scan-to-scan differences under 1 Hz for most subjects. Paired t-tests indicated a significant difference only in PRESS NAAG between the two thalamus scans (p=0.002). T2 correction based on shorter T2 values showed better agreement to the dual-TE water integral ratio. Conclusions: ISTHMUS facilitated and standardized acquisition and post-processing and reduced operator workload to eliminate potential human error.

Integrated Short-TE and Hadamard-edited Multi-Sequence (ISTHMUS) for advanced MRS.

BACKGROUND: To examine data quality and reproducibility using ISTHMUS, which has been implemented as the standardized MR spectroscopy sequence for the multi-site Healthy Brain and Child Development (HBCD) study. METHODS: ISTHMUS is the consecutive acquisition of short-TE PRESS (32 transients) and long-TE HERCULES (224 transients) data with dual-TE water reference scans. Voxels were positioned in the centrum semiovale, dorsal anterior cingulate cortex, posterior cingulate cortex and bilateral thalamus regions. After acquisition, ISTHMUS data were separated into the PRESS and HERCULES portions for analysis and modeled separately using Osprey. In vivo experiments were performed in 10 healthy volunteers (6 female; 29.5±6.6 years). Each volunteer underwent two scans on the same day. Differences in metabolite measurements were examined. T2 correction based on the dual-TE water integrals were compared with: 1) T2 correction based on the default white matter and gray matter T2 reference values in Osprey and 2) shorter WM and GM T2 values from recent literature. RESULTS: No significant difference in linewidth was observed between PRESS and HERCULES. Bilateral thalamus spectra had produced significantly higher (p<0.001) linewidth compared to the other three regions. Linewidth measurements were similar between scans, with scan-to-scan differences under 1 Hz for most subjects. Paired t-tests indicated a significant difference only in PRESS NAAG between the two thalamus scans (p=0.002). T2 correction based on shorter T2 values showed better agreement to the dual-TE water integral ratio. CONCLUSIONS: ISTHMUS facilitated data acquisition and post-processing and reduced operator workload to eliminate potential human error.

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.

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.

Multiplexing experiments in NMR and multi-nuclear MRI.

Multiplexing NMR experiments by direct detection of multiple free induction decays (FIDs) in a single experiment offers a dramatic increase in the spectral information content and often yields significant improvement in sensitivity per unit time. Experiments with multi-FID detection have been designed with both homonuclear and multinuclear acquisition, and the advent of multiple receivers on commercial spectrometers opens up new possibilities for recording spectra from different nuclear species in parallel. Here we provide an extensive overview of such techniques, designed for applications in liquid- and solid-state NMR as well as in hyperpolarized samples. A brief overview of multinuclear MRI is also provided, to stimulate cross fertilization of ideas between the two areas of research (NMR and MRI). It is shown how such techniques enable the design of experiments that allow structure elucidation of small molecules from a single measurement. Likewise, in biomolecular NMR experiments multi-FID detection allows complete resonance assignment in proteins. Probes with multiple RF microcoils routed to multiple NMR receivers provide an alternative way of increasing the throughput of modern NMR systems, effectively reducing the cost of NMR analysis and increasing the information content at the same time. Solid-state NMR experiments have also benefited immensely from both parallel and sequential multi-FID detection in a variety of multi-dimensional pulse schemes. We are confident that multi-FID detection will become an essential component of future NMR methodologies, effectively increasing the sensitivity and information content of NMR measurements.

Experiments with direct detection of multiple FIDs.

Pulse schemes with direct observation of multiple free induction decays (FIDs) offer a dramatic increase in the spectral information content of NMR experiments and often yield substantial improvement in measurement sensitivity per unit time. Availability of multiple receivers on the state-of-the-art commercial spectrometers allows spectra from different nuclear species to be recorded in parallel routinely. Experiments with multi-FID detection have been designed with both, homonuclear and multinuclear acquisition. We provide a brief overview of such techniques designed for applications in liquid- and solid- state NMR as well as in hyperpolarized samples. Here we show how these techniques have led to design of experiments that allow structure elucidation of small molecules and resonance assignment in proteins from a single measurement. Probes with multiple RF micro-coils routed to multiple NMR receivers provide an alternative way of increasing the throughput of modern NMR systems. Solid-state NMR experiments have also benefited immensely from both parallel and simultaneous FID acquisition in a variety of multi-dimensional pulse schemes. We believe that multi-FID detection will become an essential component of the future NMR methodologies effectively increasing the information content of NMR experiments and reducing the cost of NMR analysis.

Recording 13C-15N HMQC 2D sparse spectra in solids in 30 s.

We propose a dipolar HMQC Hadamard-encoded (D-HMQC-Hn) experiment for fast 2D correlations of abundant nuclei in solids. The main limitation of the Hadamard methods resides in the length of the encoding pulses, which results from a compromise between the selectivity and the sensitivity due to losses. For this reason, these methods should mainly be used with sparse spectra, and they profit from the increased separation of the resonances at high magnetic fields. In the case of the D-HMQC-Hn experiments, we give a simple rule that allows directly setting the optimum length of the selective pulses, versus the minimum separation of the resonances in the indirect dimension. The demonstration has been performed on a fully 13C,15N labelled f-MLF sample, and it allowed recording the build-up curves of the 13C-15N cross-peaks within 10 min. However, the method could also be used in the case of less sensitive samples, but with more accumulations.

Local T2 measurement employing longitudinal Hadamard encoding and adiabatic inversion pulses in porous media.

Band selective adiabatic inversion radio frequency pulses were employed for multi-slice T2 distribution measurements in porous media samples. Multi-slice T2 measurement employing longitudinal Hadamard encoding has an inherent sensitivity advantage over slice-by-slice local T2 measurements. The slice selection process is rendered largely immune to B1 variation by employing hyperbolic secant adiabatic inversion pulses, which simultaneously invert spins in several well-defined slices. While Hadamard encoding is well established for local spectroscopy, the current work is the first use of Hadamard encoding for local T2 measurement.