Identifying the source of spurious signals caused by B 0 inhomogeneities in single-voxel 1H 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 (B 0 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 B 0 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 B 0 map where the signal dephasing due to external (crusher) and internal (B 0 ) 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 B 0 map. This can facilitate MRS sequence design to be less sensitive to experimental artifacts

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 &lt; 0.05). APTw values were higher in pLGG subtype pilocytic astrocytoma compared with other pLGG subtypes (p &lt; 0.05). Non-invasive characterization of pediatric brain tumor biology with APTw imaging could aid the radiologist in clinical decision-making.</p

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

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

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

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

Glutamate levels across deep brain structures in patients with a psychotic disorder and its relation to cognitive functioning

BACKGROUND: Patients with psychotic disorders often show prominent cognitive impairment. Glutamate seems to play a prominent role, but its role in deep gray matter (DGM) regions is unclear. AIMS: To evaluate glutamate levels within deep gray matter structures in patients with a psychotic disorder in relation to cognitive functioning, using advanced spectroscopic acquisition, reconstruction, and post-processing techniques. METHODS: A 7-Tesla magnetic resonance imaging scanner combined with a lipid suppression coil and subject-specific water suppression pulses was used to acquire high-resolution magnetic resonance spectroscopic imaging data. Tissue fraction correction and registration to a standard brain were performed for group comparison in specifically delineated DGM regions. The brief assessment of cognition in schizophrenia was used to evaluate cognitive status. RESULTS: Average glutamate levels across DGM structures (i.e. caudate, pallidum, putamen, and thalamus) in mostly medicated patients with a psychotic disorder ( n  = 16, age = 33, 4 females) were lower compared to healthy controls ( n  = 23, age = 24, 7 females; p  = 0.005, d  = 1.06). Stratified analyses showed lower glutamate levels in the caudate ( p  = 0.046, d  = 0.76) and putamen p  = 0.013, d  = 0.94). These findings were largely explained by age differences between groups. DGM glutamate levels were positively correlated with psychomotor speed ( r(30) = 0.49, p  = 0.028), but not with other cognitive domains. CONCLUSIONS: We find reduced glutamate levels across DGM structures including the caudate and putamen in patients with a psychotic disorder that are linked to psychomotor speed. Despite limitations concerning age differences, these results underscore the potential role of detailed in vivo glutamate assessments to understand cognitive deficits in psychotic disorders

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

Advanced intraoperative MRI in pediatric brain tumor surgery

Introduction: In the pediatric brain tumor surgery setting, intraoperative MRI (ioMRI) provides "real-time" imaging, allowing for evaluation of the extent of resection and detection of complications. The use of advanced MRI sequences could potentially provide additional physiological information that may aid in the preservation of healthy brain regions. This review aims to determine the added value of advanced imaging in ioMRI for pediatric brain tumor surgery compared to conventional imaging. Methods: Our systematic literature search identified relevant articles on PubMed using keywords associated with pediatrics, ioMRI, and brain tumors. The literature search was extended using the snowball technique to gather more information on advanced MRI techniques, their technical background, their use in adult ioMRI, and their use in routine pediatric brain tumor care. Results: The available literature was sparse and demonstrated that advanced sequences were used to reconstruct fibers to prevent damage to important structures, provide information on relative cerebral blood flow or abnormal metabolites, or to indicate the onset of hemorrhage or ischemic infarcts. The explorative literature search revealed developments within each advanced MRI field, such as multi-shell diffusion MRI, arterial spin labeling, and amide-proton transfer-weighted imaging, that have been studied in adult ioMRI but have not yet been applied in pediatrics. These techniques could have the potential to provide more accurate fiber tractography, information on intraoperative cerebral perfusion, and to match gadolinium-based T1w images without using a contrast agent. Conclusion: The potential added value of advanced MRI in the intraoperative setting for pediatric brain tumors is to prevent damage to important structures, to provide additional physiological or metabolic information, or to indicate the onset of postoperative changes. Current developments within various advanced ioMRI sequences are promising with regard to providing in-depth tissue information

Comparison of 2-Hydroxyglutarate Detection With sLASER and MEGA-sLASER at 7T

The onco-metabolite 2-hydroxyglutarate (2HG), a biomarker of IDH-mutant gliomas, can be detected with 1H MR spectroscopy (1H-MRS). Recent studies showed measurements of 2HG at 7T with substantial gain in signal to noise ratio (SNR) and spectral resolution, offering higher specificity and sensitivity for 2HG detection. In this study, we assessed the sensitivity of semi-localized by adiabatic selective refocusing (sLASER) and J-difference MEsher-GArwood-semi-LASER (MEGA-sLASER) for 2HG detection at 7T. We performed spectral editing at long TE using a TE-optimized sLASER sequence (110 ms) and J-difference spectroscopy using MEGA-sLASER (TE = 74ms) in phantoms with different 2HG concentrations to assess the sensitivity of 2HG detection. The robustness of the methods against B0 inhomogeneity was investigated. Moreover, the performance of these two techniques was evaluated in four patients with IDH1-mutated glioma. In contrary to MEGA-sLASER, sLASER was able to detect 2HG concentration as low as 0.5 mM. In case of a composite phantom containing 2HG with overlapping metabolites, MEGA-sLASER provided a clean 2HG signal with higher fitting reliability (lower %CRLB). The results demonstrate that sLASER is more robust against field inhomogeneities and experimental or motion-related artifacts which promotes to adopt sLASER in clinical implementations