Point-resolved Spectroscopy Pulse Sequence Research Articles

Investigating the effects of aerobic exercise primed anodal transcranial direct current stimulation on γ‐aminobutyric acid concentrations in mild vascular cognitive impairment

AbstractBackgroundMild vascular cognitive impairment (mVCI) is characterized by minor deficits in cognition and memory due to underlying vascular pathology. Anodal transcranial direct current stimulation (atDCS), a non‐invasive neuromodulation technique, has been demonstrated to improve cognition. The effects of atDCS have been suggested to be mediated by γ‐aminobutyric acid (GABA)–a major inhibitory neurotransmitter associated with cerebral perfusion and oxygenation, and cognition and memory. However, previous studies have reported mixed results regarding changes in GABA concentrations following atDCS. Physical activity has been reported to increase cortical GABA levels, and in particular, aerobic exercise (AE) is associated with improved cognition in older adults. Preliminary data from an ongoing trial (EXPRESS‐V) was used to evaluate whether GABA concentration in the motor cortex was altered following AE and/or atDCS and whether this was associated with changes in global cognition in mVCI.MethodIn this double‐blind, randomized clinical trial, participants received one of four interventions for two weeks: AE and atDCS, AE and sham atDCS, exercise education and atDCS, or exercise education and sham atDCS. mVCI was determined based on a modified Gorelick criteria. At baseline and endpoint, GABA concentration in the motor cortex was measured using magnetic resonance spectroscopy and quantified with the Mescher‐Garwood point resolved spectroscopy pulse sequence, and global cognition was assessed using the Montreal Cognitive Assessment. Wilcoxon signed rank test was used to determine changes in GABA concentrations (ΔGABA). Spearman correlation was used to determine the association between ΔGABA and changes in global cognition (ΔMoCA).ResultTen participants have enrolled so far, with nine participants having completed the study (22.2% female, age = 66.4(9.8), years of education = 8.8(3.4), 55.6% White, baseline MoCA score = 22.8(3.1)). To date, ΔGABA was insignificant between baseline and endpoint (Z = 23.0, p = 0.953). However, a positive trend between ΔGABA and ΔMoCA was observed (ρ = 0.650, p = 0.058).ConclusionPreliminary results from nine participants showed a positive trend between ΔGABA and ΔMoCA. Since the trial is ongoing, with the target of recruiting 80 participants by 2024, analyses on unblinded data upon study completion will determine whether AE and atDCS leads to greater ΔGABA, and whether this is accompanied by greater ΔMoCA in mVCI.

A method for cranial target delineation in radiotherapy treatment planning aided by single-voxel magnetic resonance spectroscopy: evaluation using a custom-designed gel-based phantom and simulations.

Magnetic resonance spectroscopy (MRS) has been useful in radiotherapy treatment planning (RTP) especially in tumor delineation. Routinely, 2D/3D MRSI data are used for this application. However, not all centers have access to 2D/3D MRSI. The objective of this study was to introduce a method of using single-voxel spectroscopy (SVS) data in target delineation and assess its reliability. A gel-based phantom containing Creatine (Cr), N-acetyl-l-aspartic-acid (NAA), and Choline (Cho) was designed and built. The metabolite ratios simulate the normal and tumoral part of the brain. The jMRUI software (v. 6.0) was used to simulate a 1.5 T GE MRI scanner. The metabolite spectra provided by different time of echos (TE)s of the Point-RESolved Spectroscopy pulse-sequence (PRESS), different data-points, and post-processings were quantized by jMRUI. PseudoMRSI maps of Cho/Cr, NAA/Cr, and Cho + Cr/NAA were created. A conformity index (CI) was used to determine which metabolite-ratio isolines are more appropriate for tumor delineation. The simulation accuracy was verified. There were no differences > 4% between the measured and simulated spectra in peak regions. The pseudoMRSI map of Cho + Cr/NAA smoothly followed the complicated geometry of the tumor inside the gel-based phantom. The results showed that the single-voxel spectra produced by the PRESS pulse sequence with the TE of 144 ms, 512 data-points, and minimum post-processings of water suppression, eddy current correction, and baseline correction can be used for target delineation. This study suggests that SVS data can be used to aid target delineation by using a mathematical approach. This can enable a wider use of MR-derived information in radiotherapy. To the best of our knowledge, until now, 2D or 3D MRSI data provided from 3T MRI scanners have been used for MRS-based radiotherapy treatment planning. However, there are a lot of centers that are equipped to 1.5 T MRI scanners and some of them just equipped to SVS. This study introduces a mathematical approach to help these centers to take the benefits of MRS-based treatment planning.

Slice-selective broadband refocusing pulses for the robust generation of crushed spin-echoes

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 B1 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.

An in vivo proton neurospectroscopy study of cerebral oxidative stress in myalgic encephalomyelitis (chronic fatigue syndrome)

A particularly important family of antioxidant defence enzymes in the body are the glutathione peroxidases, which remove H 2O 2 by coupling its reduction to H 2O with oxidation of reduced glutathione (GSH) to oxidised glutathione (GSSG). There are suggestions that GSH in the peripheral blood may be reduced in myalgic encephalomyelitis, which is a highly disabling neurological disease of unknown aetiology. Since many of the symptoms relate to cerebral functioning, it would seem probable that peripheral blood GSH findings would be reflected in lower cerebral GSH levels. The aim of this study was to carry out the first direct assessment of cerebral GSH levels in myalgic encephalomyelitis; the hypothesis being tested was that cerebral GSH levels would be reduced in myalgic encephalomyelitis. Cerebral proton neurospectroscopy was carried out at a magnetic field strength of 3 T in 26 subjects; spectra were obtained from 20×20×20 mm 3 voxels using a point-resolved spectroscopy pulse sequence. The mean cerebral GSH level in the myalgic encephalomyelitis patients was 2.703 (SD 2.311) which did not differ significantly from that in age- and gender-matched normal controls who did not have any history of neurological or other major medical disorder (5.191, SD 8.984; NS). Therefore our study does not suggest that GSH is reduced in the brain in myalgic encephalomyelitis. At the present time, based on the results of this study, there is no evidence to support the suggestion that, by taking glutathione supplements, an improvement in the brain-related symptomatology of myalgic encephalomyelitis may occur.

P02-06 Dementia in Alzheimer’s disease: A comparison of MRI and 1H-MRS findings between Alzheimer’s disease and mild cognitive impairment

Aim:To compare Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (1H-MRS) between people with Alzheimer's disease (AD) and mild cognitive impairment (MCI).Background review:AD is characterised by cognitive impairment. 10-15% of people with MCI progress to dementia each year. The hippocampus is involved in memory functioning and is one of the brain regions first affected by AD. MRI based hippocampal volumetric measurement enables accurate quantification of atrophy. In addition, 1H-MRS can be used to measure concentrations of brain metabolites including myoinositol (mI) and N-acetylaspartate (NAA). NAA is a proxy measure of neuronal density.Method:Subjects with AD (n=46), MCI (n=28) and controls (n=39) were scanned using a 1.5 Tesla MR system. Manual tracing of hippocampal volumes was undertaken using Measure software. 1H-MRS voxels of interest were defined in the left and right hippocampi. A point-resolved spectroscopy pulse sequence produced spectra from each voxel and clearly resolved NAA and mI peaks. Statistical analysis was undertaken using SPSS15.Results:Hippocampal volumes were significantly reduced between AD and controls (p=0.003) and between AD and MCI (p=0.001). Compared to controls, individuals with AD and MCI had a significant reduction in [NAA]. MCI showed a non-significant increase in [mI]. A positive relationship was found between hippocampal volume and [NAA] and between hippocampal volume and [mI] for MCI.Conclusions:AD is associated with decreased viable neuronal density/function (as measured by NAA) and a reduction in hippocampal volume associated with impaired cognitive functioning. The elevated [mI] in MCI may be a “tipping point” into dementia.

Interleaving Gradient Magnetic Field Method for Diffusion Weighted Spectroscopy

Diffusion-weighted magnetic resonance spectroscopy (DWS) has considerable potential in clinical and research applications. However, it is seldom implemented in conventional magnetic resonance imaging (MRI) scanners due to the strict hardware requirements. We propose an interleaving gradient magnetic field (IGMF) method based on point resolved spectroscopy (PRESS). Four interlaced powerful diffusion sensitive gradient magnetic fields are positioned around the two π refocusing rf pulses in the PRESS sequence. This method utilizes the interval time in the PRESS pulse sequence, doubles the duration time of the diffusion sensitive gradient magnetic field and decreases the detrimental effect of the induced eddy current. The results of theoretical analysis and experimental observation demonstrate that the IGMF method is suitable for conventional MRI scanners.

Three-dimensional Proton MR Spectroscopy of Human Prostate at 3 T without Endorectal Coil: Feasibility

To evaluate sensitivity and specificity of proton magnetic resonance (MR) spectroscopy of the prostate with external surface coil elements at 3 T for differentiation of cancer from healthy tissue within an acceptable measurement time, by using histopathologic findings as the reference standard. The study was approved by the institutional review board; informed consent was obtained. Forty-five men (age range, 51-70 years) underwent 3-T MR imaging with external radiofrequency surface coils for signal reception. MR spectroscopy was performed with acquisition-weighted three-dimensional water- and lipid-suppressed point-resolved spectroscopy pulse sequence. Voxels were classified into healthy peripheral zone, central gland, and periurethral zone and cancer tissue. Cancer voxels were classified according to cancer size and certainty in matching histopathologic findings with MR images. After visual inspection of automated fitting of classified voxels, the choline plus creatine-to-citrate (Cho + Cr/Cit) ratio was calculated for all tissues. Area under the receiver operating characteristic curves (A(z)) values were used to assess accuracy of discrimination of cancer from healthy tissues. P < .05 indicated a significant difference. After exclusion of four patients with no voxels that passed visual inspection of the automated fit, a median of 82% of the classified voxels per patient was used in the analysis. Mean Cho + Cr/Cit ratios for healthy tissues were 0.22 +/- 0.12 (standard deviation) for peripheral zone, 0.34 +/- 0.14 for central gland, and 0.36 +/- 0.20 for periurethral area; all were significantly different from that of cancer (P < .001). A(z) for discrimination of probable and definite cancer tissue from healthy tissue for the peripheral zone (0.84) was significantly higher than that for the central gland (0.69) (P < .05). Three-dimensional proton MR spectroscopy of the prostate, with a combination of only external radiofrequency surface coils at 3 T, can be used to discriminate cancer from healthy tissue.

Clinical 1h magnetic resonance spectroscopy of brain metastases at 1.5T and 3T

To investigate whether improvements in signal-to-noise ratio (SNR) and spectral resolution are found in spectra from patients with brain metastases obtained at higher magnetic field strengths using standard clinical instrumentation. Six patients with brain metastases, 13 healthy volunteers, and a phantom containing brain metabolites were examined using two clinical MR instruments operating at 1.5T (Siemens) and 3T (Philips) with standard clinical head coils. Spectra were obtained using a point resolved spectroscopy pulse sequence, echo times (TE) 32 ms and 144 ms, and repetition time 2000 ms from a volume-of-interest (VOI) of size 15 x 15 x 15 mm3. SNR and spectral resolution of the metabolites N-acetylaspartate, choline, and creatine compounds in spectra from 3T were compared to the 1.5T spectra. In general, spectral resolution was improved by 25-30% at higher magnetic field strength. Only minor improvements in SNR were obtained at 3T using short echo time and 20-50% at long echo time. SNR and spectral resolution were improved at higher magnetic field strength, especially with TE 144 ms, including spectra from patients with heterogeneous brain tumors. However, differences in the defined effective VOI, particularly at short echo time, reduced the expected effect of increased magnetic field strength on the measured SNR.

Removal of the outer lines of the citrate multiplet in proton magnetic resonance spectra of the prostatic gland by accurate timing of a point-resolved spectroscopy pulse sequence.

Proton MR spectra of a healthy human prostatic gland show a major signal for citrate appearing as an AB-type multiplet. After application of multipulse localization sequences, the outer lines of this multiplet often appear with dispersion line shapes disturbing the baseline and interfering with proper quantification of citrate itself and other nearby resonances. Based upon analytical descriptions of the time evaluation of an AB spin system during a point resolved spectroscopy (PRESS) pulse sequence (90x-tau 1-180y-tau 2-180y-t), equations were derived representing the intensity of the absorption and dispersion line shape of the outer lines of the citrate multiplet at the top of echo t = tau 2-tau 1. From these equations, it was calculated that the outer lines of citrate can be removed almost completely using a PRESS pulse sequence with tau 1 = 11 ms and tau 2 = 60 ms. The theoretical description was confirmed by the almost complete disappearance of the two outer citrate resonances in in vitro and in vivo proton MR spectra acquired with this pulse sequence timing.

1H magnetic resonance spectroscopy characterization of neuronal dysfunction in drug-neive, chronic schizophrenia

We investigated the proton metabolism of right prefrontal white matter in drug-naive, chronic schizophrenic patients (n = 23), compared with healthy normal control subjects (n = 10), by using localized, water-suppressed in vivo 1H magnetic resonance (MR) spectroscopy. All 1H MR spectroscopy examinations were performed on a 1.5-T MR imaging/MR spectroscopy system by using a point-resolved spectroscopy pulse sequence for localized volumes of 2 x 2 x 2 cm3. Proton metabolite ratios relative to creatine (Cr) were obtained using a Marquart algorithm. Drug-naive, chronic schizophrenic patients demonstrated a decrease in the N-acetylaspartate (NAA):Cr and choline (Cho):Cr ratios and an increase of the complex of gamma-aminobutyric acid (GABA) and glutamate (Glu)-containing ratio [(GABA + Glu):Cr] as compared with normal control subjects. Results suggest that the reduction of NAA and Cho may indicate neuronal dysfunction and that the elevation of GABA and Glu may play a role in chronic schizophrenia. 1H MR spectroscopy may be a useful modality in research and in the clinical evaluation of chronic schizophrenic patients.