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This study aimed to implement a multimodal 1H/HP-13C imaging protocol to augment the serial monitoring of patients with glioma, while simultaneously pursuing methods for improving the robustness of HP-13C metabolic data. A total of 100 1H/HP [1-13C]-pyruvate MR examinations (104 HP-13C datasets) were acquired from 42 patients according to the comprehensive multimodal glioma imaging protocol. Serial data coverage, accuracy of frequency reference, and acquisition delay were evaluated using a mixed-effects model to account for multiple exams per patient. Serial atlas-based HP-13C MRI demonstrated consistency in volumetric coverage measured by inter-exam dice coefficients (0.977 ± 0.008, mean ± SD; four patients/11 exams). The atlas-derived prescription provided significantly improved data quality compared to manually prescribed acquisitions (n = 26/78; p = 0.04). The water-based method for referencing [1-13C]-pyruvate center frequency significantly reduced off-resonance excitation relative to the coil-embedded [13C]-urea phantom (4.1 ± 3.7 Hz vs. 9.9 ± 10.7 Hz; p = 0.0007). Significantly improved capture of tracer inflow was achieved with the 2-s versus 5-s HP-13C MRI acquisition delay (p = 0.007). This study demonstrated the implementation of a comprehensive multimodal 1H/HP-13C MR protocol emphasizing the monitoring of steady-state/dynamic metabolism in patients with glioma.
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PURPOSE: Investigate the possibility of measuring changes in glutathione (GSH) concentration using the MRS PRESS and MEGA-PRESS sequences by tracking the natural oxidation of GSH, and to examine the accuracy of the two methods. METHODS: 122 GSH edited MEGA-PRESS and PRESS acquisitions were acquired on a "braino" based phantom +3.0â¯mM GSH during a period of 11â¯days. All spectra were analyzed in LCModel. (The MEGA-PRESS data were first preprocessed in Matlab). Degradation curves were modeled. A one year follow-up on the same phantom and measurements from a similar phantom without GSH and one pure GSH phantom were also included. RESULTS: Both MEGA-PRESS and PRESS showed degradation of the measured GSH signal. Modeling the exponential decay of the GSH signal in MEGA-PRESS and PRESS gave for tâ¯=â¯0; 2.9 i.u. for MEGA-PRESS and 2.3 i.u. for PRESS. As t increased, the GSH concentration converged to zero for MEGA-PRESS but not for PRESS (0.7 i.u.). GSH for the one year follow up were 0.0 i.u. for MEGA-PRESS and 0.6 i.u. for PRESS. Similar phantom without GSH yielded 0.0 i.u. for both MEGA-PRESS and PRESS. CONCLUSION: It is possible to measure changes in GSH concentration in a phantom using both PRESS and MEGA-PRESS techniques, however the PRESS spectrum appears to include oxidized GSH (GSSG). In addition, GSH edited MEGA-PRESS measurement gives more precise values at lower GSH concentrations.
Assuntos
Glutationa/química , Espectroscopia de Ressonância Magnética , Oxigênio/química , Antioxidantes/química , Encéfalo/diagnóstico por imagem , Radicais Livres , Dissulfeto de Glutationa/química , Humanos , NADP/química , Imagens de Fantasmas , Substâncias Redutoras/química , Reprodutibilidade dos Testes , Razão Sinal-RuídoRESUMO
Spectral editing allows direct measurement of low-concentration metabolites, such as GABA, glutathione (GSH) and lactate (Lac), relevant for understanding brain (patho)physiology. The most widely used spectral editing technique is MEGA-PRESS, which has been diversely implemented across research sites and vendors, resulting in variations in the final resolved edited signal. In this paper, we describe an effort to develop a new universal MEGA-PRESS sequence with HERMES functionality for the major MR vendor platforms with standardized RF pulse shapes, durations, amplitudes and timings. New RF pulses were generated for the universal sequence. Phantom experiments were conducted on Philips, Siemens, GE and Canon 3â¯T MRI scanners using 32-channel head coils. In vivo experiments were performed on the same six subjects on Philips and Siemens scanners, and on two additional subjects, one on GE and one on Canon scanners. On each platform, edited MRS experiments were conducted with the vendor-native and universal MEGA-PRESS sequences for GABA (TEâ¯=â¯68â¯ms) and Lac editing (TEâ¯=â¯140â¯ms). Additionally, HERMES for GABA and GSH was performed using the universal sequence at TEâ¯=â¯80â¯ms. The universal sequence improves inter-vendor similarity of GABA-edited and Lac-edited MEGA-PRESS spectra. The universal HERMES sequence yields both GABA- and GSH-edited spectra with negligible levels of crosstalk on all four platforms, and with strong agreement among vendors for both edited spectra. In vivo GABA+/Cr, Lac/Cr and GSH/Cr ratios showed relatively low variation between scanners using the universal sequence. In conclusion, phantom and in vivo experiments demonstrate successful implementation of the universal sequence across all four major vendors, allowing editing of several metabolites across a range of TEs.
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Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/normas , Adulto , Feminino , Glutationa/metabolismo , Humanos , Ácido Láctico/metabolismo , Espectroscopia de Ressonância Magnética/instrumentação , Masculino , Ácido gama-Aminobutírico/metabolismoRESUMO
Glutamate is the most abundant excitatory neurotransmitter in the human brain, but in vivo imaging of acute fluctuations in glutamatergic levels has not been well established. The purpose of this study was to examine acute changes in glutamate after stimulation with N-acetylcysteine (NAC) using a simultaneous positron emission tomography/magnetic resonance spectroscopy (PET/MRS) approach. Ten healthy adult males were examined in two scanning sessions, and 5g NAC was administered 1 h prior to one of the scan sessions. Simultaneous PET/MR data were acquired using an integrated 3T PET/MR scanner. Glutamate (Glu), glutamine (Gln), and glutamate + glutamine (Glx) levels were assessed from MRS data collected from the basal ganglia with PRESS and from the left prefrontal cortex with PRESS and MEGAPRESS, and mGluR5 binding (BPND) was assessed from PET data collected with [18F]PSS232. NAC administration was associated with a significant reduction in Glx and Gln in the basal ganglia spectra, and in Glx in the frontal MEGAPRESS spectra (pâ¯<â¯0.05); no differences in [18F]PSS232 BPND were observed with NAC, although a correlation between pre-/post-treatment Glx and baseline BPnd was found. The MRS-visible Glx signal is sensitive to acute fluctuations in glutamate. The change in Glx was mostly driven by a change in Gln, lending weight to the notion that Gln can provide a proxy marker for neurotransmitter/synaptic glutamate. [18F]PSS232 binding is not sensitive to acute glutamate shifts independently, but was associated with the extent of glutamate liberation upon NAC stimulation.
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Acetilcisteína/administração & dosagem , Gânglios da Base/metabolismo , Ácido Glutâmico/metabolismo , Córtex Pré-Frontal/metabolismo , Adulto , Gânglios da Base/efeitos dos fármacos , Glutamina/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Tomografia por Emissão de Pósitrons , Córtex Pré-Frontal/efeitos dos fármacos , Adulto JovemRESUMO
MR spectroscopic imaging (MRSI) at ultra-high field (≥7 T) benefits from improved sensitivity that allows the detection of low-concentration metabolites in the brain. However, optimized acquisition techniques are required to overcome inherent limitations of MRSI at ultra-high field. This work describes an optimized method for fast high-resolution 1 H-MRSI of the brain at 7 T. The proposed acquisition sequence combines precise volume localization using semi-localization by adiabatic selective refocusing, fast spatial encoding using high-bandwidth symmetric echo-planar spectroscopic imaging (EPSI), and robust water suppression with variable power and optimized relaxation delays. This showed improved robustness to B0 and B1+ inhomogeneities, eddy currents, nuisance signal contamination and system instabilities. Furthermore, a method for correction of phase inconsistencies in symmetric EPSI enabled high-bandwidth measurements at 7 T. The proposed correction effectively removed spectral ghosting using a single-shot water reference scan. This framework was tested in healthy volunteers at 7 T and spectral quality was compared with lower-spatial-resolution scans, measured at 3 T using the same methodology. A gain in the signal-to-noise ratio (SNR) per unit volume and unit time of 1.57 was achieved, keeping acquisition time short (5 min) and the specific absorption rate within the permitted limits. This SNR enhancement obtained at ultra-high field enabled high-resolution (0.25-0.375 mL) metabolite mapping of the brain within a clinically feasible scan time. The correlation of the reconstructed maps with anatomical structures was observed, showing the diagnostic potential of the technique.
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Imagem Ecoplanar , Colina/metabolismo , Creatina/metabolismo , Humanos , Processamento de Imagem Assistida por Computador , Espectroscopia de Ressonância Magnética , Metaboloma , Razão Sinal-RuídoRESUMO
BACKGROUND: The majority of WHO grades II and III gliomas harbor a missense mutation in the metabolic gene isocitrate dehydrogenase (IDH) and accumulate the metabolite R-2-hydroxyglutarate (R-2HG). Prior studies showed that this metabolite can be detected in vivo using proton magnetic-resonance spectroscopy (MRS), but the sensitivity of this methodology and its clinical implications are unknown. METHODS: We developed an MR imaging protocol to integrate 2HG-MRS into routine clinical glioma imaging and examined its performance in 89 consecutive glioma patients. RESULTS: Detection of 2-hydroxyglutarate (2HG) in IDH-mutant gliomas was closely linked to tumor volume, with sensitivity ranging from 8% for small tumors (<3.4 mL) to 91% for larger tumors (>8 mL). In patients undergoing 2HG-MRS prior to surgery, tumor levels of 2HG corresponded with tumor cellularity but not with tumor grade or mitotic index. Cytoreductive therapy resulted in a gradual decrease in 2HG levels with kinetics that closely mirrored changes in tumor volume. CONCLUSIONS: Our study demonstrates that 2HG-MRS can be linked with routine MR imaging to provide quantitative measurements of 2HG in glioma and may be useful as an imaging biomarker to monitor the abundance of IDH-mutant tumor cells noninvasively during glioma therapy and disease monitoring.
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Neoplasias Encefálicas/patologia , Glioma/patologia , Glutaratos/metabolismo , Isocitrato Desidrogenase/metabolismo , Guias de Prática Clínica como Assunto , Espectroscopia de Prótons por Ressonância Magnética/métodos , Adulto , Idoso , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/terapia , Feminino , Seguimentos , Glioma/metabolismo , Glioma/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Adulto JovemRESUMO
PURPOSE: Modern magnetic resonance imaging scanners with high-performance gradient systems have high maximum gradient strength (Gmax ) and slew rate (Smax ). Peripheral nerve stimulation (PNS) is often a more limiting factor for gradient waveform design than Gmax and Smax . Traditionally, the slew rate is derated globally to adhere to PNS limitations. METHODS: In this work, the PNS limitation is already included in the gradient waveform design in the form of a time-varying slew rate, hence shortening the overall gradient duration. RESULTS: Spiral and echo-planar imaging trajectories were designed with a multitude of parameters, and it was demonstrated that trajectory durations from conventional to PNS-optimal design can be shortened by 8 and 3%, respectively. CONCLUSION: Including PNS-limits in the gradient waveform design can shorten the duration of gradient trajectories, thereby reducing associated artifacts.
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Campos Magnéticos/efeitos adversos , Imageamento por Ressonância Magnética/efeitos adversos , Modelos Neurológicos , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/fisiopatologia , Nervos Periféricos/fisiopatologia , Simulação por Computador , Estimulação Elétrica/efeitos adversos , Humanos , Traumatismos dos Nervos Periféricos/prevenção & controle , Nervos Periféricos/efeitos da radiação , Doses de RadiaçãoRESUMO
A major challenge for in vivo magnetic resonance spectroscopy with point-resolved spectroscopy (PRESS) is the low signal intensity for the measurement of weakly scalar coupled spins, for example lactate. The chemical-shift displacement error between the two coupling partners of the lactate molecule leads to a signal decrease. The chemical-shift displacement error is decreased and therefore the lactate signal is increased by using refocusing pulses with a broad bandwidth. Previously, slice-selective broadband universal rotation pulses (S-BURBOP) were designed and applied as refocusing pulses in the PRESS pulse sequence (Janich MA, et al., Journal of Magnetic Resonance, 2011, 213, 126-135). However, S-BURBOP pulses leave a phase error across the slice which is superimposed on the spectra when spatially resolving the PRESS voxel. In the present novel design of slice-selective broadband refocusing pulses (S-BREBOP) this phase error is avoided. S-BREBOP pulses obtain 2.5 times the bandwidth of conventional Shinnar-Le Roux pulses and are robust against ±20% miscalibration of the B(1) amplitude. S-BREBOP pulses were validated in phantoms and in a low-grade brain tumor of a patient. Compared to conventional Shinnar-Le Roux pulses they lead to a decrease of the chemical-shift displacement error and consequently a lactate signal increase.