•White matter abnormalities are frequently observed in persons with schizophrenia.•Low n-acetylaspartate could disrupt white matter by preventing myelin synthesis.•People with schizophrenia had lower ...n-acetylaspartate than healthy controls.•Lower n-acetylaspartate levels predicted worse white matter integrity in patients, unaffected relatives and controls.•Neural levels of n-acetylaspartate appear to be related to white matter integrity.
Compromised white matter has been reported in schizophrenia; however, few studies have investigated neurochemical abnormalities underlying microstructural differences. N-acetylaspartate (NAA) is used to synthesize myelin and is often reduced in persons with schizophrenia (PSZ) and their unaffected first-degree relatives (REL). Low levels of NAA could affect white matter by preventing the synthesis or repair of myelin. We used magnetic resonance spectroscopy and diffusion tensor imaging to investigate the relationship between NAA and white matter integrity in PSZ. REL were included to examine whether putative relationships are associated with symptom expression or illness liability. 52 controls, 23 REL and 25 PSZ underwent 7T proton magnetic resonance spectroscopy and/or 3T diffusion tensor imaging. NAA in the visual cortex and basal ganglia were measured and compared across groups. Diffusivity measures were compared across groups using tract-based spatial statistics and related to NAA concentrations. Visual cortex NAA was significantly reduced in PSZ compared to controls. White matter integrity did not differ between groups. Reduced cortical and subcortical NAA were associated with diffusivity measures of poor white matter microstructure. These data suggest that levels of neural NAA may be related to white matter integrity similarly across individuals with schizophrenia, those at genetic risk, and controls.
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.
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.
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 1H MRS using a B0 map. This can facilitate MRS sequence design to be less sensitive to experimental artifacts.
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.
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.
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).
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.
Registration number, NL49333.041.14/ NTR4980 . Registered on 16 October 2014.
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 β) 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‐β, 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.
Ethanolamine kinase‐1 (Etnk‐1) was identified as a major cause of elevated phosphoethanolamine (PE) in breast cancer and pancreatic cancer cells. Downregulation of Etnk‐1 with siRNA resulted in cell cytotoxicity that correlated with PE levels. Etnk‐1 may provide a potential diagnostic and therapeutic target in breast and pancreatic cancers.
Cortical glutamate in migraine Zielman, Ronald; Wijnen, Jannie P; Webb, Andrew ...
Brain (London, England : 1878),
2017-Jul-01, 2017-07-01, 20170701, Volume:
140, Issue:
7
Journal Article
Peer reviewed
Open access
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.
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