A silent echo-planar spectroscopic imaging readout with high spectral bandwidth MRSI using an ultrasonic gradient axis.

PURPOSE: We present a novel silent echo-planar spectroscopic imaging (EPSI) readout, which uses an ultrasonic gradient insert to accelerate MRSI while producing a high spectral bandwidth (20 kHz) and a low sound level. METHODS: The ultrasonic gradient insert consisted of a single-axis (z-direction) plug-and-play gradient coil, powered by an audio amplifier, and produced 40 mT/m at 20 kHz. The silent EPSI readout was implemented in a phase-encoded MRSI acquisition. Here, the additional spatial encoding provided by this silent EPSI readout was used to reduce the number of phase-encoding steps. Spectroscopic acquisitions using phase-encoded MRSI, a conventional EPSI-readout, and the silent EPSI readout were performed on a phantom containing metabolites with resonance frequencies in the ppm range of brain metabolites (0-4 ppm). These acquisitions were used to determine sound levels, showcase the high spectral bandwidth of the silent EPSI readout, and determine the SNR efficiency and the scan efficiency. RESULTS: The silent EPSI readout featured a 19-dB lower sound level than a conventional EPSI readout while featuring a high spectral bandwidth of 20 kHz without spectral ghosting artifacts. Compared with phase-encoded MRSI, the silent EPSI readout provided a 4.5-fold reduction in scan time. In addition, the scan efficiency of the silent EPSI readout was higher (82.5% vs. 51.5%) than the conventional EPSI readout. CONCLUSIONS: We have for the first time demonstrated a silent spectroscopic imaging readout with a high spectral bandwidth and low sound level. This sound reduction provided by the silent readout is expected to have applications in sound-sensitive patient groups, whereas the high spectral bandwidth could benefit ultrahigh-field MR systems.

Amide proton transfer weighted imaging in pediatric neuro-oncology: initial experience.

Amide proton transfer weighted (APTw) imaging enables in vivo assessment of tissue-bound mobile proteins and peptides through the detection of chemical exchange saturation transfer. Promising applications of APTw imaging have been shown in adult brain tumors. As pediatric brain tumors differ from their adult counterparts, we investigate the radiological appearance of pediatric brain tumors on APTw imaging. APTw imaging was conducted at 3 T. APTw maps were calculated using magnetization transfer ratio asymmetry at 3.5 ppm. First, the repeatability of APTw imaging was assessed in a phantom and in five healthy volunteers by calculating the within-subject coefficient of variation (wCV). APTw images of pediatric brain tumor patients were analyzed retrospectively. APTw levels were compared between solid tumor tissue and normal-appearing white matter (NAWM) and between pediatric high-grade glioma (pHGG) and pediatric low-grade glioma (pLGG) using t-tests. APTw maps were repeatable in supratentorial and infratentorial brain regions (wCV ranged from 11% to 39%), except those from the pontine region (wCV between 39% and 50%). APTw images of 23 children with brain tumor were analyzed (mean age 12 years ± 5, 12 male). Significantly higher APTw values are present in tumor compared with NAWM for both pHGG and pLGG (p < 0.05). APTw values were higher in pLGG subtype pilocytic astrocytoma compared with other pLGG subtypes (p < 0.05). Non-invasive characterization of pediatric brain tumor biology with APTw imaging could aid the radiologist in clinical decision-making.

Improving advanced intraoperative MRI methods during pediatric neurosurgery.

Advanced intraoperative MR images (ioMRI) acquired during the resection of pediatric brain tumors could offer additional physiological information to preserve healthy tissue. With this work, we aimed to develop a protocol for ioMRI with increased sensitivity for arterial spin labeling (ASL) and diffusion MRI (dMRI), optimized for patient positioning regularly used in the pediatric neurosurgery setting. For ethical reasons, ASL images were acquired in healthy adult subjects that were imaged in the prone and supine position. After this, the ASL cerebral blood flow (CBF) was quantified and compared between both positions. To evaluate the impact of the RF coils setups on image quality, we compared different setups (two vs. four RF coils) by looking at T1-weighted (T1w) signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), as well as undertaking a qualitative evaluation of T1w, T2w, ASL, and dMR images. Mean ASL CBF did not differ between the surgical prone and supine positions in any of the investigated regions of interest or the whole brain. T1w SNR (gray matter: p = 0.016, 34% increase; white matter: p = 0.016, 32% increase) and CNR were higher (p = 0.016) in the four versus two RF coils setups (18.0 ± 1.8 vs. 13.9 ± 1.8). Qualitative evaluation of T1w, T2w, ASL, and dMR images resulted in acceptable to good image quality and did not differ statistically significantly between setups. Only the nonweighted diffusion image maps and corticospinal tract reconstructions yielded higher image quality and reduced susceptibility artifacts with four RF coils. Advanced ioMRI metrics were more precise with four RF coils as the standard deviation decreased. Taken together, we have investigated the practical use of advanced ioMRI during pediatric neurosurgery. We conclude that ASL CBF quantification in the surgical prone position is valid and that ASL and dMRI acquisition with two RF coils can be performed adequately for clinical use. With four versus two RF coils, the SNR of the images increases, and the sensitivity to artifacts reduces.

Deuterium echo-planar spectroscopic imaging (EPSI) in the human liver in vivo at 7 T.

PURPOSE: To demonstrate the feasibility of deuterium echo-planar spectroscopic imaging (EPSI) to accelerate 3D deuterium metabolic imaging in the human liver at 7 T. METHODS: A deuterium EPSI sequence, featuring a Hamming-weighted k-space acquisition pattern for the phase-encoding directions, was implemented. Three-dimensional deuterium EPSI and conventional MRSI were performed on a water/acetone phantom and in vivo in the human liver at natural abundance. Moreover, in vivo deuterium EPSI measurements were acquired after oral administration of deuterated glucose. The effect of acquisition time on SNR was evaluated by retrospectively reducing the number of averages. RESULTS: The SNR of natural abundance deuterated water signal in deuterium EPSI was 6.5% and 5.9% lower than that of MRSI in the phantom and in vivo experiments, respectively. In return, the acquisition time of in vivo EPSI data could be reduced retrospectively to 2 min, beyond the minimal acquisition time of conventional MRSI (of 20 min in this case), while still leaving sufficient SNR. Three-dimensional deuterium EPSI, after administration of deuterated glucose, enabled monitoring of hepatic glucose dynamics with full liver coverage, a spatial resolution of 20 mm isotropic, and a temporal resolution of 9 min 50 s, which could retrospectively be shortened to 2 min. CONCLUSION: In this work, we demonstrate the feasibility of accelerated 3D deuterium metabolic imaging of the human liver using deuterium EPSI. The acceleration obtained with EPSI can be used to increase temporal and/or spatial resolution, which will be valuable to study tissue metabolism of deuterated compounds over time.

Identifying the source of spurious signals caused by B0 inhomogeneities in single-voxel 1 H MRS.

PURPOSE: Single-voxel MRS (SV MRS) requires robust volume localization as well as optimized crusher and phase-cycling schemes to reduce artifacts arising from signal outside the volume of interest. However, due to local magnetic field gradients (B0 inhomogeneities), signal that was dephased by the crusher gradients during acquisition might rephase, leading to artifacts in the spectrum. Here, we analyzed this mechanism, aiming to identify the source of signals arising from unwanted coherence pathways (spurious signals) in SV MRS from a B0 map. METHODS: We investigated all possible coherence pathways associated with imperfect localization in a semi-localized by adiabatic selective refocusing (semi-LASER) sequence for potential rephasing of signals arising from unwanted coherence pathways by a local magnetic field gradient. We searched for locations in the B0 map where the signal dephasing due to external (crusher) and internal (B0 ) field gradients canceled out. To confirm the mechanism, SV-MR spectra (TE = 31 ms) and 3D-CSI data with the same volume localization as the SV experiments were acquired from a phantom and 2 healthy volunteers. RESULTS: Our analysis revealed that potential sources of spurious signals were scattered over multiple locations throughout the brain. This was confirmed by 3D-CSI data. Moreover, we showed that the number of potential locations where spurious signals could originate from monotonically decreases with crusher strength. CONCLUSION: We proposed a method to identify the source of spurious signals in SV 1 H MRS using a B0 map. This can facilitate MRS sequence design to be less sensitive to experimental artifacts.

The use of variable delay multipulse chemical exchange saturation transfer for separately assessing different CEST pools in the human brain at 7T.

PURPOSE: Current challenges of in vivo CEST imaging include overlapping signals from different pools. The overlap arises from closely resonating pools and/or the broad magnetization transfer contrast (MTC) from macromolecules. This study aimed to evaluate the feasibility of variable delay multipulse (VDMP) CEST to separately assess solute pools with different chemical exchange rates in the human brain in vivo, while mitigating the MTC. METHODS: VDMP saturation buildup curves were simulated for amines, amides, and relayed nuclear Overhauser effect. VDMP data were acquired from glutamate and bovine serum albumin phantoms, and from six healthy volunteers at 7T. For the in vivo data, MTC removal was performed via a three-pool Lorentzian fitting. Different B1 amplitudes and mixing times were used to evaluate CEST pools with different exchange rates. RESULTS: The results show the importance of removing MTC when applying VDMP in vivo and the influence of B1 for distinguishing different pools. Finally, the optimal B1 and mixing times to effectively saturate slow- and fast-exchanging components are also reported. Slow-exchanging amides and rNOE components could be distinguished when using B1 = 1 µT and tmix = 10 ms and 40 ms, respectively. Fast-exchanging components reached the highest saturation when using a B1 = 2.8 µT and tmix = 0 ms. CONCLUSION: VDMP is a powerful CEST-editing tool, exploiting chemical exchange-rate differences. After MTC removal, it allows separate assessment of slow- and fast-exchanging solute pools in in vivo human brain.

Proton metabolic mapping of the brain at 7 T using a two-dimensional free induction decay-echo-planar spectroscopic imaging readout with lipid suppression.

The increased signal-to-noise ratio (SNR) and chemical shift dispersion at high magnetic fields (≥7 T) have enabled neuro-metabolic imaging at high spatial resolutions. To avoid very long acquisition times with conventional magnetic resonance spectroscopic imaging (MRSI) phase-encoding schemes, solutions such as pulse-acquire or free induction decay (FID) sequences with short repetition time and inner volume selection methods with acceleration (echo-planar spectroscopic imaging [EPSI]), have been proposed. With the inner volume selection methods, limited spatial coverage of the brain and long echo times may still impede clinical implementation. FID-MRSI sequences benefit from a short echo time and have a high SNR per time unit; however, contamination from strong extra-cranial lipid signals remains a problem that can hinder correct metabolite quantification. L2-regularization can be applied to remove lipid signals in cases with high spatial resolution and accurate prior knowledge. In this work, we developed an accelerated two-dimensional (2D) FID-MRSI sequence using an echo-planar readout and investigated the performance of lipid suppression by L2-regularization, an external crusher coil, and the combination of these two methods to compare the resulting spectral quality in three subjects. The reduction factor of lipid suppression using the crusher coil alone varies from 2 to 7 in the lipid region of the brain boundary. For the combination of the two methods, the average lipid area inside the brain was reduced by 2% to 38% compared with that of unsuppressed lipids, depending on the subject's region of interest. 2D FID-EPSI with external lipid crushing and L2-regularization provides high in-plane coverage and is suitable for investigating brain metabolite distributions at high fields.

Brain proton magnetic resonance spectroscopy and neurodevelopment after preterm birth: a systematic review.

BACKGROUND: Preterm infants are at risk of neurodevelopmental impairments. At present, proton magnetic resonance spectroscopy (1H-MRS) is used to evaluate brain metabolites in asphyxiated term infants. The aim of this review is to assess associations between cerebral 1H-MRS and neurodevelopment after preterm birth. METHODS: PubMed and Embase were searched to identify studies using 1H-MRS and preterm birth. Eligible studies for this review included 1H-MRS of the brain, gestational age ≤32 weeks, and neurodevelopment assessed at a corrected age (CA) of at least 12 months up to the age of 18 years. RESULTS: Twenty papers evaluated 1H-MRS in preterm infants at an age between near-term and 18 years and neurodevelopment. 1H-MRS was performed in both white (WM) and gray matter (GM) in 12 of 20 studies. The main regions were frontal and parietal lobe for WM and basal ganglia for GM. N-acetylaspartate/choline (NAA/Cho) measured in WM and/or GM is the most common metabolite ratio associated with motor, language, and cognitive outcome at 18-24 months CA. CONCLUSIONS: NAA/Cho in WM assessed at term-equivalent age was associated with motor, cognitive, and language outcome, and NAA/Cho in deep GM was associated with language outcome at 18-24 months CA. IMPACT: In preterm born infants, brain metabolism assessed using 1H-MRS at term-equivalent age is associated with motor, cognitive, and language outcomes at 18-24 months. 1H-MRS at term-equivalent age in preterm born infants may be used as an early indication of brain development. Specific findings relating to NAA were most predictive of outcome.

GLS hyperactivity causes glutamate excess, infantile cataract and profound developmental delay.

Loss-of-function mutations in glutaminase (GLS), the enzyme converting glutamine into glutamate, and the counteracting enzyme glutamine synthetase (GS) cause disturbed glutamate homeostasis and severe neonatal encephalopathy. We report a de novo Ser482Cys gain-of-function variant in GLS encoding GLS associated with profound developmental delay and infantile cataract. Functional analysis demonstrated that this variant causes hyperactivity and compensatory downregulation of GLS expression combined with upregulation of the counteracting enzyme GS, supporting pathogenicity. Ser482Cys-GLS likely improves the electrostatic environment of the GLS catalytic site, thereby intrinsically inducing hyperactivity. Alignment of +/-12.000 GLS protein sequences from >1000 genera revealed extreme conservation of Ser482 to the same degree as catalytic residues. Together with the hyperactivity, this indicates that Ser482 is evolutionarily preserved to achieve optimal-but submaximal-GLS activity. In line with GLS hyperactivity, increased glutamate and decreased glutamine concentrations were measured in urine and fibroblasts. In the brain (both grey and white matter), glutamate was also extremely high and glutamine was almost undetectable, demonstrated with magnetic resonance spectroscopic imaging at clinical field strength and subsequently supported at ultra-high field strength. Considering the neurotoxicity of glutamate when present in excess, the strikingly high glutamate concentrations measured in the brain provide an explanation for the developmental delay. Cataract, a known consequence of oxidative stress, was evoked in zebrafish expressing the hypermorphic Ser482Cys-GLS and could be alleviated by inhibition of GLS. The capacity to detoxify reactive oxygen species was reduced upon Ser482Cys-GLS expression, providing an explanation for cataract formation. In conclusion, we describe an inborn error of glutamate metabolism caused by a GLS hyperactivity variant, illustrating the importance of balanced GLS activity.

Advanced single voxel 1 H magnetic resonance spectroscopy techniques in humans: Experts' consensus recommendations.

Conventional proton MRS has been successfully utilized to noninvasively assess tissue biochemistry in conditions that result in large changes in metabolite levels. For more challenging applications, namely, in conditions which result in subtle metabolite changes, the limitations of vendor-provided MRS protocols are increasingly recognized, especially when used at high fields (≥3 T) where chemical shift displacement errors, B0 and B1 inhomogeneities and limitations in the transmit B1 field become prominent. To overcome the limitations of conventional MRS protocols at 3 and 7 T, the use of advanced MRS methodology, including pulse sequences and adjustment procedures, is recommended. Specifically, the semiadiabatic LASER sequence is recommended when TE values of 25-30 ms are acceptable, and the semiadiabatic SPECIAL sequence is suggested as an alternative when shorter TE values are critical. The magnetic field B0 homogeneity should be optimized and RF pulses should be calibrated for each voxel. Unsuppressed water signal should be acquired for eddy current correction and preferably also for metabolite quantification. Metabolite and water data should be saved in single shots to facilitate phase and frequency alignment and to exclude motion-corrupted shots. Final averaged spectra should be evaluated for SNR, linewidth, water suppression efficiency and the presence of unwanted coherences. Spectra that do not fit predefined quality criteria should be excluded from further analysis. Commercially available tools to acquire all data in consistent anatomical locations are recommended for voxel prescriptions, in particular in longitudinal studies. To enable the larger MRS community to take advantage of these advanced methods, a list of resources for these advanced protocols on the major clinical platforms is provided. Finally, a set of recommendations are provided for vendors to enable development of advanced MRS on standard platforms, including implementation of advanced localization sequences, tools for quality assurance on the scanner, and tools for prospective volume tracking and dynamic linear shim corrections.

Brain temperature of infants with neonatal encephalopathy following perinatal asphyxia calculated using magnetic resonance spectroscopy.

BACKGROUND: Little is known about brain temperature of neonates during MRI. Brain temperature can be estimated non-invasively with proton Magnetic Resonance Spectroscopy (1H-MRS), but the most accurate 1H-MRS method has not yet been determined. The primary aim was to estimate brain temperature using 1H-MRS in infants with neonatal encephalopathy (NE) following perinatal asphyxia. The secondary aim was to compare brain temperature during MRI with rectal temperatures before and after MRI. METHODS: In this retrospective study, brain temperature in 36 (near-)term infants with NE was estimated using short (36 ms) and long (288 ms) echo time (TE) 1H-MRS. Brain temperature was calculated using two different formulas: formula of Wu et al. and a formula based on phantom calibration. The methods were compared. Rectal temperatures were collected <3 hours before and after MRI. RESULTS: Brain temperatures calculated with the formula of Wu et al. and the calibrated formula were similar as well as brain temperatures derived from short and long TE 1H-MRS. Rectal temperature did not differ before and after MRI. CONCLUSIONS: Brain temperature can be measured using 1H-MRS in daily clinical practice using the formula of Wu et al. with both short and long TE 1H-MRS. Brain temperature remained within physiological range during MRI.

Early detection of changes in phospholipid metabolism during neoadjuvant chemotherapy in breast cancer patients using phosphorus magnetic resonance spectroscopy at 7T.

The purpose of this work was to investigate whether noninvasive early detection (after the first cycle) of response to neoadjuvant chemotherapy (NAC) in breast cancer patients was possible. 31 P-MRSI at 7 T was used to determine different phosphor metabolites ratios and correlate this to pathological response. 31 P-MRSI was performed in 12 breast cancer patients treated with NAC. 31 P spectra were fitted and aligned to the frequency of phosphoethanolamine (PE). Metabolic signal ratios for phosphomonoesters/phosphodiesters (PME/PDE), phosphocholine/glycerophosphatidylcholine (PC/GPtC), phosphoethanolamine/glycerophosphoethanolamine (PE/GPE) and phosphomonoesters/in-organic phosphate (PME/Pi) were determined from spectral fitting of the individual spectra and the summed spectra before and after the first cycle of NAC. Metabolic ratios were subsequently related to pathological response. Additionally, the correlation between the measured metabolic ratios and Ki-67 levels was determined using linear regression. Four patients had a pathological complete response after treatment, five patients a partial pathological response, and three patients did not respond to NAC. In the summed spectrum after the first cycle of NAC, PME/Pi and PME/PDE decreased by 18 and 13%, respectively. A subtle difference among the different response groups was observed in PME/PDE, where the nonresponders showed an increase and the partial and complete responders a decrease (P = 0.32). No significant changes in metabolic ratios were found. However, a significant association between PE/Pi and the Ki-67 index was found (P = 0.03). We demonstrated that it is possible to detect subtle changes in 31 P metabolites with a 7 T MR system after the first cycle of NAC treatment in breast cancer patients. Nonresponders showed different changes in metabolic ratios compared with partial and complete responders, in particular for PME/PDE; however, more patients need to be included to investigate its clinical value.

Shortening of apparent transverse relaxation time of inorganic phosphate as a breast cancer biomarker.

Phosphorus MRS offers a non-invasive tool for monitoring cell energy and phospholipid metabolism and can be of additional value in diagnosing cancer and monitoring cancer therapy. In this study, we determined the transverse relaxation times of a number of phosphorous metabolites in a group of breast cancer patients by adiabatic multi-echo spectroscopic imaging at 7 T. The transverse relaxation times of phosphoethanolamine, phosphocholine, inorganic phosphate (Pi ), glycerophosphocholine and glycerophosphatidylcholine were 184 ± 8 ms, 203 ± 17 ms, 87 ± 8 ms, 240 ± 56 ms and 20 ± 10 ms, respectively. The transverse relaxation time of Pi in breast cancer tissue was less than half that of healthy fibroglandular tissue. This effect is most likely caused by an up-regulation of glycolysis in breast cancer tissue that leads to interaction of Pi with the GAPDH enzyme, which forms part of the reversible pathway of exchange of Pi with gamma-adenosine tri-phosphate, thus shortening its apparent transverse relaxation time. As healthy breast tissue shows very little glycolytic activity, the apparent T2 shortening of Pi due to malignant transformation could possibly be used as a biomarker for cancer.

Homogeneous B1+ for bilateral breast imaging at 7 T using a five dipole transmit array merged with a high density receive loop array.

To explore the use of five meandering dipole antennas in a multi-transmit setup, combined with a high density receive array for breast imaging at 7 T for improved penetration depth and more homogeneous B1 field. Five meandering dipole antennas and 30 receiver loops were positioned on two cups around the breasts. Finite difference time domain simulations were performed to evaluate RF safety limits of the transmit setup. Scattering parameters of the transmit setup and coupling between the antennas and the detuned loops were measured. In vivo parallel imaging performance was investigated for various acceleration factors. After RF shimming, a B1 map, a T1 -weighted image, and a T2 -weighted image were acquired to assess B1 efficiency, uniformity in contrast weighting, and imaging performance in clinical applications. The maximum achievable local SAR10g value was 7.0 W/kg for 5 × 1 W accepted power. The dipoles were tuned and matched to a maximum reflection of -11.8 dB, and a maximum inter-element coupling of -14.2 dB. The maximum coupling between the antennas and the receive loops was -18.2 dB and the mean noise correlation for the 30 receive loops 7.83 ± 8.69%. In vivo measurements showed an increased field of view, which reached to the axilla, and a high transmit efficiency. This coil enabled the acquisition of T1 -weighted images with a high spatial resolution of 0.7 mm3 isotropic and T2 -weighted spin echo images with uniformly weighted contrast.

Contradiction between amide-CEST signal and pH in breast cancer explained with metabolic MRI.

PURPOSE: Metabolic MRI is a noninvasive technique that can give new insights into understanding cancer metabolism and finding biomarkers to evaluate or monitor treatment plans. Using this technique, a previous study has shown an increase in pH during neoadjuvant chemotherapy (NAC) treatment, while recent observation in a different study showed a reduced amide proton transfer (APT) signal during NAC treatment (negative relation). These findings are counterintuitive, given the known intrinsic positive relation of APT signal to pH. METHODS: In this study we combined APT MRI and 31 P-MRSI measurements to unravel the relation between the APT signal and pH in breast cancer. Twenty-two breast cancer patients were scanned with a 7 T MRI before and after the first cycle of NAC treatment. pH was determined by the chemical shift of inorganic phosphate (Pi). RESULTS: While APT signals have a positive relation to pH and amide content, we observed a direct negative linear correlation between APT signals and pH in breast tumors in vivo. CONCLUSIONS: As differentiation of cancer stages was confirmed by observation of a linear correlation between cell proliferation marker PE/Pi (phosphoethanolamine over inorganic phosphate) and pH in the tumor, our data demonstrates that the concentration of mobile proteins likely supersedes the contribution of the exchange rate to the APT signal.

Amide chemical exchange saturation transfer at 7 T: a possible biomarker for detecting early response to neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: The purpose of this work was to investigate noninvasive early detection of treatment response of breast cancer patients to neoadjuvant chemotherapy (NAC) using chemical exchange saturation transfer (CEST) measurements sensitive to amide proton transfer (APT) at 7 T. METHODS: CEST images were acquired in 10 tumors of nine breast cancer patients treated with NAC. APT signals in the tumor, before and after the first cycle of NAC, were quantified using a three-pool Lorentzian fit of the z-spectra in the region of interest. The changes in APT were subsequently related to pathological response after surgery defined by the Miller-Payne system. RESULTS: Significant differences (P <  0.05, unpaired Mann-Whitney test) were found in the APT signal before and after the first cycle of NAC in six out of 10 lesions, of which two showed a pathological complete response. Of the remaining four lesions, one showed a pathological complete response. No significant difference in changes of APT signal were found between the different pathological responses to NAC treatment (P > 0.05, Kruskal-Wallis test). CONCLUSIONS: This preliminary study shows the feasibility of using APT CEST magnetic resonance imaging as a noninvasive biomarker to assess the effect of NAC in an early stage of NAC treatment of breast cancer patients. TRIAL REGISTRATION: Registration number, NL49333.041.14/ NTR4980 . Registered on 16 October 2014.

31 P T2 s of phosphomonoesters, phosphodiesters, and inorganic phosphate in the human brain at 7T.

PURPOSE: To determine the phosphorus-31 T2 s of phosphomonoesters, phosphodiesters, and inorganic phosphate in the healthy human brain at 7T. METHODS: A 3D chemical shift imaging multi-echo sequence with composite block pulses for refocusing was used to measure one free induction decay (FID) and seven full echoes with an echo spacing of 45 ms on the brain of nine healthy volunteers (age range 22-45 years; average age 27 ± 8 years). Spectral fitting was used to determine the change in metabolic signal amplitude with echo time. RESULTS: The average apparent T2 s with their standard deviation were 202 ± 6 ms, 129 ± 6 ms, 86 ± 2 ms, 214 ± 10 ms, and 213 ± 11 ms for phosphoethanolamine, phosphocholine, inorganic phosphate, glycerophosphoethanolamine, and glycerophosphocholine, respectively. CONCLUSION: The determined apparent T2 for phosphoethanolamine, glycerophosphocholine, and glycerophosphoethanolamine is approximately 200 ms. The lower apparent T2 value for phosphocholine is attributed to the overlap of this resonance with the 3-phosphorous resonance of 2,3-diphosphoglycerate from blood, with an apparent shorter T2 . Omitting the FID signal and the first echo of phosphocholine leads to a T2 of 182 ± 7 ms, whereas a biexponential analysis leads to 203 ± 4 ms. These values are more in line with phosphoethanolamine and the phosphodiesters. The short T2 of inorganic phosphate is subscribed to the fast reversible exchange with γ-adenosine triphosphate, which is mediated by glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase within the glycolytic pathway. Magn Reson Med 80:29-35, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Tailored spiral in-out spectral-spatial water suppression pulses for magnetic resonance spectroscopic imaging.

PURPOSE: To develop short water suppression sequences for 7 T magnetic resonance spectroscopic imaging, with mitigation of subject-specific transmit RF field ( B1+) inhomogeneity. METHODS: Patient-tailored spiral in-out spectral-spatial saturation pulses were designed for a three-pulse WET water suppression sequence. The pulses' identical spatial subpulses were designed using patient-specific B1+ maps and a spiral in-out excitation k-space trajectory. The subpulse train was weighted by a spectral envelope that was root-flipped to minimize peak RF demand. The pulses were validated in in vivo experiments that acquired high resolution magnetic resonance spectroscopic imaging data, using a crusher coil for fast lipid suppression. Residual water signals and MR spectra were compared between the proposed tailored sequence and a conventional WET sequence. RESULTS: Replacing conventional spectrally-selective pulses with tailored spiral in-out spectral-spatial pulses reduced mean water residual from 5.88 to 2.52% (57% improvement). Pulse design time was less then 0.4 s. The pulses' specific absorption rate were compatible with magnetic resonance spectroscopic imaging TRs under 300 ms, which enabled spectra of fine in plane spatial resolution (5 mm) with good quality to be measured in 7.5 min. CONCLUSION: Tailored spiral in-out spectral-spatial water suppression enables efficient high resolution magnetic resonance spectroscopic imaging in the brain. Magn Reson Med 79:31-40, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Molecular causes of elevated phosphoethanolamine in breast and pancreatic cancer cells.

Elevated phosphoethanolamine (PE) is frequently observed in MRS studies of human cancers and xenografts. The role of PE in cell survival and the molecular causes underlying this increase are, however, relatively underexplored. In this study, we investigated the roles of ethanolamine kinases (Etnk-1 and 2) and choline kinases (Chk-α and ß) in contributing to increased PE in human breast and pancreatic cancer cells. We investigated the effect of silencing Etnk-1 and Etnk-2 on cell viability as a potential therapeutic strategy. Both breast and pancreatic cancer cells showed higher PE compared with their nonmalignant counterparts. We identified Etnk-1 as a major cause of the elevated PE levels in these cancer cells, with little or no contribution from Chk-α, Chk-ß, or Etnk-2. The increase of PE observed in pancreatic cancer cells in culture was replicated in the corresponding tumor xenografts. Downregulation of Etnk-1 with siRNA resulted in cell cytotoxicity that correlated with PE levels in breast and pancreatic cancer cells. Etnk-1 may provide a potential therapeutic target in breast and pancreatic cancers.

Cortical glutamate in migraine.

Cortical hyperexcitability due to enhanced glutamatergic activity has been implicated in migraine pathophysiology but direct evidence is lacking. Here we assessed glutamate levels and intracellular mobility of glutamate in the visual cortex of migraineurs in-between attacks. We included 50 migraineurs (23 with aura and 27 without aura) and 24 age- and gender-matched non-headache controls. We used proton magnetic resonance spectroscopy (1H-MRS) and diffusion weighted spectroscopy at 7 T with a single volume of interest (2 × 2 × 3 cm) located in the primary and secondary visual cortex. For 1H-MRS we used a semi-LASER sequence with water referencing for absolute quantification. For diffusion weighted spectroscopy we used an adapted PRESS sequence with gradients applied in three directions and two different gradient amplitudes. Between-group differences were evaluated using analysis of covariance with the grey matter fraction in the volume of interest as covariate and post hoc comparisons with Bonferroni correction. Glutamate concentrations differed between groups (P = 0.047) and were higher in migraineurs without aura (mean ± standard deviation: 7.02 ± 0.50 mM) compared to controls (mean ± standard deviation: 6.40 ± 0.78 mM, P = 0.042). The apparent diffusion coefficient of glutamate was similar among groups (P = 0.129) suggesting similar inter- and intracellular mobility of glutamate in all three study groups. No differences were observed for concentrations and diffusion constants of other metabolites. The present study suggests that interictal glutamate levels are increased in the visual cortex of migraineurs without aura, supporting the hypothesis of cortical hyperexcitability in migraine.