Introduction of ultra-high-field MR brain imaging in infants: vital parameters, temperature and comfort.

Background: Brain MRI in infants at ultra-high-field scanners might improve diagnostic quality, but safety should be evaluated first. In our previous study, we reported simulated specific absorption rates and acoustic noise data at 7 Tesla. Methods: In this study, we included twenty infants between term-equivalent age and three months of age. The infants were scanned on a 7 Tesla MRI directly after their clinically indicated 3 Tesla brain MRI scan. Vital parameters, temperature, and comfort were monitored throughout the process. Brain temperature was estimated during the MRI scans using proton MR spectroscopy. Results: We found no significant differences in vital parameters, temperature, and comfort during and after 7 Tesla MRI scans, compared to 3 Tesla MRI scans. Conclusions: These data confirm our hypothesis that scanning infants at 7 Tesla MRI appears to be safe and we identified no additional risks from scanning at 3 Tesla MRI.

Introduction of Ultra-High-Field MR Imaging in Infants: Preparations and Feasibility.

BACKGROUND AND PURPOSE: Cerebral MR imaging in infants is usually performed with a field strength of up to 3T. In adults, a growing number of studies have shown added diagnostic value of 7T MR imaging. 7T MR imaging might be of additional value in infants with unexplained seizures, for example. The aim of this study was to investigate the feasibility of 7T MR imaging in infants. We provide information about the safety preparations and show the first MR images of infants at 7T. MATERIALS AND METHODS: Specific absorption rate levels during 7T were simulated in Sim4life using infant and adult models. A newly developed acoustic hood was used to guarantee hearing protection. Acoustic noise damping of this hood was measured and compared with the 3T Nordell hood and no hood. In this prospective pilot study, clinically stable infants, between term-equivalent age and the corrected age of 3 months, underwent 7T MR imaging immediately after their standard 3T MR imaging. The 7T scan protocols were developed and optimized while scanning this cohort. RESULTS: Global and peak specific absorption rate levels in the infant model in the centered position and 50-mm feet direction did not exceed the levels in the adult model. Hearing protection was guaranteed with the new hood. Twelve infants were scanned. No MR imaging-related adverse events occurred. It was feasible to obtain good-quality imaging at 7T for MRA, MRV, SWI, single-shot T2WI, and MR spectroscopy. T1WI had lower quality at 7T. CONCLUSIONS: 7T MR imaging is feasible in infants, and good-quality scans could be obtained.

Acute stress effects on GABA and glutamate levels in the prefrontal cortex: A 7T 1H magnetic resonance spectroscopy study.

There is ample evidence that the inhibitory GABA and the excitatory glutamate system are essential for an adequate response to stress. Both GABAergic and glutamatergic brain circuits modulate hypothalamus-pituitary-adrenal (HPA)-axis activity, and stress in turn affects glutamate and GABA levels in the rodent brain. However, studies examining stress-induced GABA and glutamate levels in the human brain are scarce. Therefore, we investigated the influence of acute psychosocial stress (using the Trier Social Stress Test) on glutamate and GABA levels in the medial prefrontal cortex of 29 healthy male individuals using 7 Tesla proton magnetic resonance spectroscopy. In vivo GABA and glutamate levels were measured before and 30 min after exposure to either the stress or the control condition. We found no associations between psychosocial stress or cortisol stress reactivity and changes over time in medial prefrontal glutamate and GABA levels. GABA and glutamate levels over time were significantly correlated in the control condition but not in the stress condition, suggesting that very subtle differential effects of stress on GABA and glutamate across individuals may occur. However, overall, acute psychosocial stress does not appear to affect in vivo medial prefrontal GABA and glutamate levels, at least this is not detectable with current practice 1H-MRS.

Detection of lactate in the striatum without contamination of macromolecules by J-difference editing MRS at 7T.

Lactate levels are measurable by MRS and are related to neural activity. Therefore, it is of interest to accurately measure lactate levels in the basal ganglia networks. If sufficiently stable, lactate measurements may be used to investigate alterations in dopaminergic signalling in the striatum, facilitating the detection and diagnosis of metabolic deficits. The aim of this study is to provide a J-difference editing MRS technique for the selective editing of lactate only, thus allowing the detection of lactate without contamination of overlapping macromolecules. As a validation procedure, macromolecule nulling was combined with J-difference editing, and this was compared with J-difference editing with a new highly selective editing pulse. The use of a high-field (7T) MR scanner enables the application of editing pulses with very narrow bandwidth, which are selective for lactate. We show that, despite the sensitivity to B0 offsets, the use of a highly selective editing pulse is more efficient for the detection of lactate than the combination of a broad-band editing pulse with macromolecule nulling. Although the signal-to-noise ratio of uncontaminated lactate detection in healthy subjects is relatively low, this article describes the test-retest performance of lactate detection in the striatum when using highly selective J-difference editing MRS at 7 T. The coefficient of variation, σw and intraclass correlation coefficients for within- and between-subject differences of lactate were determined. Lactate levels in the left and right striatum were determined twice in 10 healthy volunteers. Despite the fact that the test-retest performance of lactate detection is moderate with a coefficient of variation of about 20% for lactate, these values can be used for the design of new studies comparing, for example, patient populations with healthy controls.

Multi-center reproducibility of neurochemical profiles in the human brain at 7 T.

The purpose of this work was to harmonize data acquisition and post-processing of single voxel proton MRS ((1) H-MRS) at 7 T, and to determine metabolite concentrations and the accuracy and reproducibility of metabolite levels in the adult human brain. This study was performed in compliance with local institutional human ethics committees. The same seven subjects were each examined twice using four different 7 T MR systems from two different vendors using an identical semi-localization by adiabatic selective refocusing spectroscopy sequence. Neurochemical profiles were obtained from the posterior cingulate cortex (gray matter, GM) and the corona radiata (white matter, WM). Spectra were analyzed with LCModel, and sources of variation in concentrations ('subject', 'institute' and 'random') were identified with a variance component analysis. Concentrations of 10-11 metabolites, which were corrected for T1 , T2 , magnetization transfer effects and partial volume effects, were obtained with mean Cramér-Rao lower bounds below 20%. Data variances and mean concentrations in GM and WM were comparable for all institutions. The primary source of variance for glutamate, myo-inositol, scyllo-inositol, total creatine and total choline was between subjects. Variance sources for all other metabolites were associated with within-subject and system noise, except for total N-acetylaspartate, glutamine and glutathione, which were related to differences in signal-to-noise ratio and in shimming performance between vendors. After multi-center harmonization of acquisition and post-processing protocols, metabolite concentrations and the sizes and sources of their variations were established for neurochemical profiles in the healthy brain at 7 T, which can be used as guidance in future studies quantifying metabolite and neurotransmitter concentrations with (1) H-MRS at ultra-high magnetic field.

Silencing of the glycerophosphocholine phosphodiesterase GDPD5 alters the phospholipid metabolite profile in a breast cancer model in vivo as monitored by (31) P MRS.

Abnormal choline phospholipid metabolism is an emerging hallmark of cancer, which is implicated in carcinogenesis and tumor progression. The malignant metabolic phenotype is characterized by high levels of phosphocholine (PC) and relatively low levels of glycerophosphocholine (GPC) in aggressive breast cancer cells. Phosphorus ((31) P) MRS is able to non-invasively detect these water-soluble metabolites of choline as well as ethanolamine phospholipid metabolism. Here we have investigated the effects of stably silencing glycerophosphoester diesterase domain containing 5 (GDPD5), which is an enzyme with glycerophosphocholine phosphodiesterase activity, in MDA-MB-231 breast cancer cells and orthotopic tumor xenografts. Tumors in which GDPD5 was stably silenced with GDPD5-specific shRNA contained increased levels of GPC and phosphoethanolamine (PE) compared with control tumors.

(31)P magnetic resonance spectroscopy of the breast and the influence of the menstrual cycle.

Phosphorus metabolite ratios are potential biomarkers in breast cancer diagnosis and treatment monitoring. Our purpose was to investigate the metabolite ratios phosphomonoester to phosphodiester, phosphoethanolamine (PE) to glycerophosphoethanolamine (GPE), and phosphocholine (PC) to glycerophosphocholine (GPC) in glandular breast tissue, and the potential effect of the menstrual cycle, using (31)P magnetic resonance spectroscopy (MRS) at 7T. Seven women with regular menstrual cycles each underwent four examinations using a 3D (31)P multi-echo magnetic resonance spectroscopic imaging sequence. Peak integrals were assessed using IDL and JMRUI software. First, T2 relaxation times were calculated using multi-echo data pooled across subjects and time points. Subsequent, metabolite ratios were calculated for each phase of the menstrual cycle using the calculated T2 values to account for when combining the free induction decay and all five echoes. The metabolite ratios were calculated both on group level and individually. T2 decay fits resulted in a T2 relaxation time for PE of 154 ms (95 % CI 144-164), for PC of 173 ms (95 % CI 148-205), for Pi of 188 ms (95 % CI 182-193), for GPE of 48 ms (95 % CI 44-53), and for GPC of 23 ms (95 % CI 21-26). The metabolite ratios analyzed on group level showed negligible variation throughout the menstrual cycle. Individual results did show an apparent intra-individual variation; however, not significant due to the measurements' uncertainty. To conclude, phospholipids in glandular tissue as measured with (31)P MRS at 7 T are not significantly affected by the menstrual cycle.

Improved efficiency on editing MRS of lactate and γ-aminobutyric acid by inclusion of frequency offset corrected inversion pulses at high fields.

γ-Aminobutyric acid (GABA) and lactate are metabolites which are present in the brain. These metabolites can be indicators of psychiatric disorders or tumor hypoxia, respectively. The measurement of these weakly coupled spin systems can be performed using MRS editing techniques; however, at high field strength, this can be challenging. This is due to the low available B1 (+) field at high fields, which results in narrow-bandwidth refocusing pulses and, consequently, in large chemical shift displacement artifacts. In addition, as a result of the increased chemical shift displacement artifacts and chemical shift dispersion, the efficiency of the MRS method is reduced, even when using adiabatic refocusing pulses. To overcome this limitation, frequency offset corrected inversion (FOCI) pulses have been suggested as a mean to substantially increase the bandwidth of adiabatic pulses. In this study, a Mescher-Garwood semi-localization by adiabatic selection and refocusing (MEGA-sLASER) editing sequence with refocusing FOCI pulses is presented for the measurement of GABA and lactate in the human brain. Metabolite detection efficiencies were improved by 20% and 75% for GABA and lactate, respectively, when compared with editing techniques that employ adiabatic radiofrequency refocusing pulses. The highly efficient MEGA-sLASER sequence with refocusing FOCI pulses is an ideal and robust MRS editing technique for the measurement of weakly coupled metabolites at high field strengths.

Quantitative short echo time 1H MRSI of the peripheral edematous region of human brain tumors in the differentiation between glioblastoma, metastasis, and meningioma.

PURPOSE: To assess metabolite levels in peritumoral edematous (PO) and surrounding apparently normal (SAN) brain regions of glioblastoma, metastasis, and meningioma in humans with (1)H-MRSI to find biomarkers that can discriminate between tumors and characterize infiltrative tumor growth. MATERIALS AND METHODS: Magnetic resonance (MR) spectra (semi-LASER MRSI, 30 msec echo time, 3T) were selected from regions of interest (ROIs) under MRI guidance, and after quality control of MR spectra. Statistical testing between patient groups was performed for mean metabolite ratios of an entire ROI and for the highest value within that ROI. RESULTS: The highest ratios of the level of choline compounds and the sum of myo-inositol and glycine over N-acetylaspartate and creatine compounds were significantly increased in PO regions of glioblastoma versus that of metastasis and meningioma. In the SAN region of glioblastoma some of these ratios were increased. Differences were less prominent for metabolite levels averaged over entire ROIs. CONCLUSION: Specific metabolite ratios in PO and SAN regions can be used to discriminate glioblastoma from metastasis and meningioma. An analysis of these ratios averaged over entire ROIs and those with most abnormal values indicates that infiltrative tumor growth in glioblastoma is inhomogeneous and extends into the SAN region.

Increase in SNR for 31P MR spectroscopy by combining polarization transfer with a direct detection sequence.

The sensitivity of (31)P MRS can be increased using higher magnetic fields, but also by using (1)H to (31)P polarization transfer techniques where the sensitivity is determined by the polarization of the proton spins and thus the signal-to-noise per unit time is unaffected by the slow T(1) relaxation properties of the (31)P spins. This implies that (31)P spins can be manipulated during the T(1) relaxation of the (1)H spins without affecting the signal-to-noise of the (1)H to (31)P polarization transferred spins. It is shown here that by combining (1)H to (31)P polarization transfer with a direct (31)P detection sequence in one repetition time, one can gain more signal-to-noise per unit of time as compared to a polarization transfer sequence alone. Proof of principle was demonstrated by phantom measurements and additionally the method was applied to the human calf muscle and to the human breast in vivo at 7 T.

7-T (1) H MRS with adiabatic refocusing at short TE using radiofrequency focusing with a dual-channel volume transmit coil.

In vivo MRS of the human brain at ultrahigh field allows for the identification of a large number of metabolites at higher spatial resolutions than currently possible in clinical practice. However, the in vivo localization of single-voxel spectroscopy has been shown to be challenging at ultrahigh field because of the low bandwidth of refocusing radiofrequency (RF) pulses. Thus far, the proposed methods for localized MRS at 7 T suffer from long TE, inherent signal loss and/or a large chemical shift displacement artifact that causes a spatial displacement between resonances, and results in a decreased efficiency in editing sequences. In this work, we show that, by driving a standard volume coil with two RF amplifiers, focusing the B 1+ field in a certain location and using high-bandwidth adiabatic refocusing pulses, a semi-LASER (semi-localized by adiabatic selective refocusing) localization is feasible at short TE in the human brain with full signal acquisition and a low chemical shift displacement artifact at 7 T.

31P magnetic resonance spectroscopic imaging with polarisation transfer of phosphomono- and diesters at 3 T in the human brain: relation with age and spatial differences.

Tissue levels of the compounds phosphocholine (PC), phosphoethanolamine (PE), glycerophosphocholine (GPC) and glycerophosphoethanolamine (GPE) can be studied by in vivo 31P MRS. However, the detection of the signals of these compounds suffers from low sensitivity and contamination by underlying broad resonances of other phosphorylated compounds. Improved sensitivity without this contamination can be achieved with a method for optimal polarisation transfer of 1H to 31P spins in these molecules, called selective refocused insensitive nuclei-enhanced polarisation transfer (sRINEPT). The aim of this study was to implement a three-dimensional magnetic resonance spectroscopic imaging (MRSI) version of sRINEPT on a clinical 3 T magnetic resonance system to obtain spatially resolved relative levels of PC, PE, GPC and GPE in the human brain as a function of age, which could be used as a reference dataset for clinical applications. Good signal-to-noise ratios were obtained from voxels of 17 cm(3) of the parietal and occipital lobes of the brain within a clinically acceptable measurement time of 17 min. Eighteen healthy subjects of different ages (16-70 years) were examined with this method. A strong inverse relation of the PE/GPE and PC/GPC ratios with age was found. Spatial resolution was sufficient to detect differences in metabolite ratios between white and grey matter. Moreover, we showed the feasibility of this method for clinical use in a pilot study of patients with brain tumours. The sRINEPT MRSI technique enables the exploration of phospholipid metabolism in brain diseases with a better sensitivity than was possible with earlier 31P MRS methods.

Efficient 1H to 31P polarization transfer on a clinical 3T MR system.

31P MR spectroscopy (MRS) in the detection of phosphocholine (PC), glycerolphosphocholine (GPC), phosphorylelthanolamine (PE), and glycerolphosphoethanolamine (GPE) compounds has shown clinical potential at 1.5T for several human diseases. The use of (1)H to (31)P polarization transfer can improve the sensitivity using a refocused INEPT method with a potential enhancement of 2.4 (gamma(1H)/gamma(31P)). However, in this method the (31)P signals of PE, PC, GPE, and GPC are strongly attenuated (50% or more) due to J-coupling between (31)P and (1)H that have similar magnitudes for homonuclear J-coupling constants in those metabolites. A method to cancel the homonuclear J-coupling effects in polarization transfer experiments is to apply frequency-selective refocusing pulses, which becomes feasible at 3T due to the increased chemical shift dispersion as compared to 1.5T. In this study, full (1)H to (31)P polarization transfer was realized using chemical shift selective refocusing pulses at 3T. T(1) and T(2) values for (1)H and (31)P spins of PE, PC, GPE, and GPC were measured in the human brain. A more than 2-fold signal-to-noise ratio (SNR) improvement was obtained compared to an optimized direct (31)P MRS method. As shifted RF pulses were used, this method can be applied on a broadband clinical MR system with a single RF system.