Localization By Adiabatic Selective Refocusing Research Articles

Scyllo-inositol: Transverse relaxation time constant at 3T and concentration changes associated with aging and alcohol use.

The goals of this study were to measure the apparent transverse relaxation time constant, T2 , of scyllo-inositol (sIns) in young and older healthy adults' brains and to investigate the effect of alcohol usage on sIns in young and older healthy adults' brains, using proton magnetic resonance spectroscopy (MRS) at 3T. Twenty-nine young adults (age 21 ± 1years) and 24 older adults (age 74 ± 3years) participated in this study. MRS data were acquired from two brain regions (the occipital cortex and posterior cingulate cortex) at 3T. The T2 of sIns was measured using a localization by adiabatic selective refocusing (LASER) sequence at various echo times, while the sIns concentrations were measured using a short-echo-time stimulated echo acquisition mode (STEAM) sequence. A trend towards lower T2 relaxation values of sIns in older adults was observed, although these were not significant. sIns concentration was higher with age in both brain regions and was significantly higher in the young when considering alcohol consumption of more than two drinks per week. This study shows that differences in sIns can be found in two distinct regions of the brain across two age groups, potentially reflecting normal aging. In addition, it is important to take into account alcohol consumption when reporting the sIns level in the brain.

Transverse relaxation time constants of the five major metabolites in human brain measured in vivo using LASER and PRESS at 3 T.

The goal of this study was to measure and compare the apparent transverse relaxation time constants (T2 ) of five intracellular metabolites using localization by adiabatic selective refocusing (LASER) and point-resolved spectroscopy (PRESS) sequences in the human brain at 3 T. Five healthy subjects were studied at 3 T. 1 H spectra from the prefrontal cortex were acquired at six different echo times using LASER and PRESS sequences. Postprocessed data were analyzed with LCModel, and the resulting amplitudes were fitted using a mono-exponential decay function to determine the T2 of metabolites. Twenty-one percent higher apparent T2 values for the singlet resonances of N-acetyl aspartate, total creatine, and total choline were measured with LASER as compared with PRESS, whereas comparable apparent T2 values were measured for strongly coupled metabolites, glutamate, and myo-inositol, with both sequences. Reliable T2 measurements were obtained with both sequences for the five major intracellular metabolites. The LASER sequence appears to be more efficient in suppressing the diffusion component for singlets (having nonexchangeable protons) compared to J-coupled metabolites. Magn Reson Med 79:1260-1265, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

3D GABA imaging with real-time motion correction, shim update and reacquisition of adiabatic spiral MRSI

Gamma-aminobutyric acid (GABA) and glutamate (Glu) are the major neurotransmitters in the brain. They are crucial for the functioning of healthy brain and their alteration is a major mechanism in the pathophysiology of many neuro-psychiatric disorders.Magnetic resonance spectroscopy (MRS) is the only way to measure GABA and Glu non-invasively in vivo. GABA detection is particularly challenging and requires special MRS techniques. The most popular is MEscher–GArwood (MEGA) difference editing with single-voxel Point RESolved Spectroscopy (PRESS) localization. This technique has three major limitations: a) MEGA editing is a subtraction technique, hence is very sensitive to scanner instabilities and motion artifacts. b) PRESS is prone to localization errors at high fields (≥3T) that compromise accurate quantification. c) Single-voxel spectroscopy can (similar to a biopsy) only probe steady GABA and Glu levels in a single location at a time.To mitigate these problems, we implemented a 3D MEGA-editing MRS imaging sequence with the following three features: a) Real-time motion correction, dynamic shim updates, and selective reacquisition to eliminate subtraction artifacts due to scanner instabilities and subject motion. b) Localization by Adiabatic SElective Refocusing (LASER) to improve the localization accuracy and signal-to-noise ratio. c) K-space encoding via a weighted stack of spirals provides 3D metabolic mapping with flexible scan times.Simulations, phantom and in vivo experiments prove that our MEGA-LASER sequence enables 3D mapping of GABA+ and Glx (Glutamate+Gluatmine), by providing 1.66 times larger signal for the 3.02ppm multiplet of GABA+ compared to MEGA-PRESS, leading to clinically feasible scan times for 3D brain imaging.Hence, our sequence allows accurate and robust 3D-mapping of brain GABA+ and Glx levels to be performed at clinical 3T MR scanners for use in neuroscience and clinical applications.

Poster #S48 THE REPRODUCIBILITY OF 1H-MRS GLUTAMATE CONCENTRATION ESTIMATES AT 3 TESLA, IMPLICATIONS FOR GLUTAMATE IMAGING IN SCHIZOPHRENIA

Gamma-aminobutyric acid (GABA) and glutamate (Glu) are the major neurotransmitters in the brain. They are crucial for the functioning of healthy brain and their alteration is a major mechanism in the pathophysiology of many neuro-psychiatric disorders.Magnetic resonance spectroscopy (MRS) is the only way to measure GABA and Glu non-invasively in vivo. GABA detection is particularly challenging and requires special MRS techniques. The most popular is MEscher–GArwood (MEGA) difference editing with single-voxel Point RESolved Spectroscopy (PRESS) localization. This technique has three major limitations: a) MEGA editing is a subtraction technique, hence is very sensitive to scanner instabilities and motion artifacts. b) PRESS is prone to localization errors at high fields (≥ 3 T) that compromise accurate quantification. c) Single-voxel spectroscopy can (similar to a biopsy) only probe steady GABA and Glu levels in a single location at a time.To mitigate these problems, we implemented a 3D MEGA-editing MRS imaging sequence with the following three features: a) Real-time motion correction, dynamic shim updates, and selective reacquisition to eliminate subtraction artifacts due to scanner instabilities and subject motion. b) Localization by Adiabatic SElective Refocusing (LASER) to improve the localization accuracy and signal-to-noise ratio. c) K-space encoding via a weighted stack of spirals provides 3D metabolic mapping with flexible scan times.Simulations, phantom and in vivo experiments prove that our MEGA-LASER sequence enables 3D mapping of GABA + and Glx (Glutamate + Gluatmine), by providing 1.66 times larger signal for the 3.02 ppm multiplet of GABA + compared to MEGA-PRESS, leading to clinically feasible scan times for 3D brain imaging.Hence, our sequence allows accurate and robust 3D-mapping of brain GABA + and Glx levels to be performed at clinical 3 T MR scanners for use in neuroscience and clinical applications.

Short‐echo, single‐shot, full‐intensity proton magnetic resonance spectroscopy for neurochemical profiling at 4 T: Validation in the cerebellum and brainstem

A short echo time (TE = 24 ms) semiadiabatic localization by adiabatic selective refocusing (LASER) sequence was designed and optimized for full-intensity proton magnetic resonance spectroscopy ((1) H MRS) at 4 T. The sequence was combined with VAPOR water suppression and three-dimensional outer volume suppression for improved localization and suppression of unwanted coherences. Artifact-free, single-shot spectra were obtained from the human brain with a spectral pattern almost identical to that obtained with an ultra-short TE (TE = 5 ms) stimulated-echo acquisition mode (STEAM) sequence as a result of the train of adiabatic refocusing pulses in semi-LASER that reduce the apparent TE. Approximately 2-fold higher signal intensity relative to STEAM was demonstrated in phantoms and the human brain. To test the performance of the sequence in clinically relevant brain regions with a volume coil, semi-LASER spectra were acquired from three cerebellar and brainstem volumes of interest (VOIs) in 23 healthy subjects. Ultra-short echo STEAM spectra were acquired from the same VOIs to compare neurochemical profiles obtained with semi-LASER with those obtained with STEAM. Neurochemical profiles of the cerebellum and brainstem acquired by these two techniques were nearly identical, validating the accuracy of the metabolite concentrations obtained with semi-LASER at the longer TE relative to STEAM. A high correlation between metabolite concentrations obtained by these two proton (1) H MRS techniques indicated the sensitivity to detect intersubject variation in metabolite levels.

Feasibility of single‐voxel MRS measurement of apparent diffusion coefficient of water in breast tumors

We report initial results with single voxel spectroscopy (SVS) using diffusion weighting and localization by adiabatic selective refocusing (LASER) in breast tumors to measure the apparent diffusion coefficient of water (ADCw). This is a quick (30 s) and relatively easy method to implement compared with image-based diffusion measurements, and is insensitive to lipid signal contamination. The ADCw and concentration of total choline containing compounds [tCho] were evaluated for associations with each other and final pathologic diagnosis in 25 subjects. The average (+/- SD) ADCw in benign and malignant lesions was 1.96 +/- 0.47 mm(2)/s and 1.26 +/- 0.29 x 10(-3) mm(2)/s, respectively, P< 0.001. Receiver operating characteristic curve analysis showed an area under the curve of 0.92. Analysis of the single voxel (SV) ADCw and [tCho] showed significant correlation with a R(2) of 0.56, P< 0.001. Compared with more commonly used image-based methods of measuring water ADC, SV-ADCw is faster, more robust, insensitive to fat, and potentially easier to implement on standard clinical systems.

Quantitative in vivo 1H spectroscopic imaging of metabolites in the early postnatal mouse brain at 17.6 T

Early postnatal brain maturation is closely connected to local changes of metabolite levels. Spatially resolved in vivo (1)H NMR spectroscopic imaging is applied to follow absolute changes of brain metabolites in early postnatal mouse brain. A short echo time semi LASER (localization by adiabatic selective refocusing) chemical shift imaging (CSI) sequence incorporating weighted k-space averaging was implemented at high magnetic field (17.6 T). In vivo measurements were carried out on postnatal days 5, 8, 12, 16, and 20. In vivo relaxation times T (1) and T (2) were measured using variable repetition times or a CPMG sequence, respectively, combined with LASER single voxel localization. Spectra were obtained with a spatial resolution of (1 x 1) mm(2) in a 1.5 mm slice as early as postnatal day 5. Maturational changes of absolute metabolite concentrations of major metabolites were calculated in four different brain regions. A significant increase of N-acetylaspartate (NAA), total creatine (tCr), and glutamate/glutamine (Glx) concentration was paralleled by a decrease of taurine (Tau) concentration with age (P < 0.05). Differences between brain regions were found for NAA, tCr, and Tau (P < 0.05). Furthermore, in vivo T (1) and T (2) of the four major brain metabolites in adult mice are reported. The implemented semi LASER CSI sequence allows following regional changes of metabolite levels. It is suitable for investigation of local differences in brain metabolism and development.

Comparison of T2 and LASER T2† image contrast in a rat model of acute cerebral ischemia

Previous studies have shown that T2(dagger)-weighted magnetic resonance images acquired using localization by adiabatic selective refocusing (LASER) can provide early tissue contrast following ischemia, possibly due to alterations in microscopic susceptibility within the tissue. The purpose of this study was to make a direct in vivo comparison of T2-, T2(dagger)- and diffusion-weighted image contrast during acute ischemia. Acute middle cerebral artery (MCA) occlusion was attempted in 14 rats using a modified Tamura approach incorporating electrocoagulation of the left MCA. T2(dagger)-weighted LASER images (Echo Time [TE]=108 ms), T2-weighted Carr-Purcell-Meiboom-Gill (CPMG) images (TE=110 ms) and diffusion-weighted images (b value=105 s/mm(2)) were acquired at 4 T within 1.5 h of ischemia onset. Tissue contrast in the MCA territory was quantified for histologically verified ischemic tissue (n=6) and in sham controls (n=4). T2(dagger)-weighted LASER images demonstrated greater contrast compared to the T2-weighted CPMG images, and more focal contrast compared to the diffusion-weighted images, suggesting different contrast mechanisms were involved.

Limits of a localized magnetic resonance spectroscopy assay for ex vivo myocardial triacylglycerol

Localized magnetic resonance spectroscopy (LMRS) promises a powerful non-invasive means to determine myocardial triacylglycerol (TAG) in a clinical setting. Here, the linearity, specificity, robustness, precision, and accuracy of an ex vivo mouse-heart LMRS TAG assay are assessed by quantifying the spatial, spectral, and relaxation-induced uncertainties. The protocol, which is based on localization by adiabatic selective refocusing (LASER) using frequency offset corrected inversion (FOCI) pulses, alternating gradient polarity, and simple post-processing, is shown to have good characteristics. The presented protocol has a benchmark, phantom-based, accuracy of 3%, and when applied to ex vivo mouse hearts the accuracy is 6%, making the LMRS assay comparable to the typical destructive bioanalytical assay.

Enhanced diffusion weighting generated by selective adiabatic pulse trains

A theoretical description and experimental validation of the enhanced diffusion weighting generated by selective adiabatic full passage (AFP) pulse trains is provided. Six phantoms (Ph-1–Ph-6) were studied on a 4 T Varian/Siemens whole body MRI system. Phantoms consisted of 2.8 cm diameter plastic tubes containing a mixture of 10 μm ORGASOL polymer beads and 2 mM Gd-DTPA dissolved in 5% agar (Ph-1) or nickel(II) ammonium sulphate hexahydrate doped (56.3–0.8 mM) water solutions (Ph-2–Ph-6). A customized localization by adiabatic selective refocusing (LASER) sequence containing slice selective AFP pulse trains and pulsed diffusion gradients applied in the phase encoding direction was used to measure 1H 2O diffusion. The b-value associated with the LASER sequence was derived using the Bloch–Torrey equation. The apparent diffusion coefficients measured by LASER were comparable to those measured by a conventional pulsed gradient spin-echo (PGSE) sequence for all phantoms. Image signal intensity increased in Ph-1 and decreased in Ph-2–Ph-6 as AFP pulse train length increased while maintaining a constant echo-time. These experimental results suggest that such AFP pulse trains can enhance contrast between regions containing microscopic magnetic susceptibility variations and homogeneous regions in which dynamic dephasing relaxation mechanisms are dominant.

1H NMR spectroscopic imaging of the mouse brain at 9.4 T

To assess the feasibility of 1H spectroscopic imaging (SI) in the mouse brain at 9.4 T, and investigate regional variations in brain metabolites. A total of 21 SI studies were performed in CD-1 mice to evaluate the basal ganglia (N=5), hippocampus and thalamus (N=11), and cerebellum (N=5). We adjusted the B0 homogeneity for each slice using a fully automated shim calculation method based on the B0 map, which we measured using a multislice gradient-echo sequence with multiple phase evolution delays. The SI employed a modified localization by adiabatic selective refocusing (LASER) sequence with TE/TR of 50/2000 msec, 24x24 encodes over a field of view (FOV) of 24 mmx24 mm, 1 microL voxel resolution, and two averages, for a total acquisition time of 38 minutes. Sufficient shimming was achieved and high-quality spectra were consistently obtained in each slice. N-acetyl aspartate (NAA)/creatine (Cr) ratios in the basal ganglia and thalamus (0.86+/-0.07, and 0.87+/-0.07, respectively) were significantly higher than those in the hippocampus and cerebellum (0.76+/-0.03 and 0.67+/-0.07), which were also significantly different from each other. 1H SI of the mouse brain is highly reproducible and allows differences in regional metabolite ratios to be easily visualized.

Experimental validation of a T2ρ transverse relaxation model using LASER and CPMG acquisitions

The transverse relaxation rate (R2=1/T2) of many biological tissues are altered by endogenous magnetized particles (i.e., ferritin, deoxyhemoglobin), and may be sensitive to the pathological progression of neurodegenerative disorders associated with altered brain-iron stores. R2 measurements using Carr–Purcell–Meiboom–Gill (CPMG) acquisitions are sensitive to the refocusing pulse interval (2τcp), and have been modeled as a chemical exchange (CE) process, while R2 measurements using a localization by adiabatic selective refocusing (LASER) sequence have an additional relaxation rate contribution that has been modeled as a R2ρ process. However, no direct comparison of the R2 measured using these two sequences has been described for a controlled phantom model of magnetized particles. The three main objectives of this study were: (1) to compare the accuracy of R2 relaxation rate predictions from the CE model with experimental data acquired using a conventional CPMG sequence, (2) to compare R2 estimates obtained using LASER and CPMG acquisitions, and (3) to determine whether the CE model, modified to account for R2ρ relaxation, adequately describes the R2 measured by LASER for a full range of τcp values. In all cases, our analysis was confined to spherical magnetic particles that satisfied the weak field regime. Three phantoms were produced that contained spherical magnetic particles (10μm diameter polyamide powders) suspended in Gd-DTPA (1.0, 1.5, and 2.0mmol/L) doped gel. Mono-exponential R2 measurements were made at 4T as a function of refocusing pulse interval. CPMG measurements of R2 agreed with CE model predictions while significant differences in R2 estimates were observed between LASER and CPMG measurements for short τcp acquisitions. The discrepancy between R2 estimates is shown to be attributable to contrast enhancement in LASER due to T2ρ relaxation.

Quantitative short echo-time1H LASER-CSI in human brain at 4 T

A novel short echo-time (1)H chemical shift imaging (CSI) pulse sequence is presented that incorporates localization by adiabatic selective refocusing (LASER) for FOV-reduction, k-space weighted averaging and macromolecule subtraction, to obtain quantitative concentration measurements of N-acetyl-aspartate, glutamate, glucose, myo-inositol, creatine and choline using a nominal voxel size of 0.56 cm(3). A comparison of spectral quality and metabolite concentration measurements was made between LASER-CSI and LASER-single voxel spectroscopy (SVS) in a region of homogeneous parietal white matter (N = 8). No significant differences were found in linewidths, signal-to-noise ratios or the effectiveness of the macromolecule subtraction between SVS and CSI. Water suppression was 45% more effective in SVS than in CSI (p < 0.05). A linear regression of all paired metabolite measurements resulted in a slope = 1.01 +/- 0.03 (r(2) = 0.73). LASER-CSI concentration measurements of N-acetyl-aspartate, glutamate, glucose, myo-inositol, creatine and choline were in agreement (within standard deviations) with LASER-SVS measurements. LASER-CSI is, therefore, a viable and attractive option for future (1)H CSI investigations.

Quantitative proton short-echo-time LASER spectroscopy of normal human white matter and hippocampus at 4 Tesla incorporating macromolecule subtraction.

Accurate quantification of in vivo short-echo-time (TE) (1)H spectra must account for contributions from both mobile metabolites and less mobile macromolecules, which can fluctuate in disease. The purpose of this study was to develop an approach for the acquisition and processing of macromolecule information to optimize metabolite quantification accuracy and precision. Human parietal white matter (8-cm(3) voxel) and posterior hippocampus (1.7-cm(3) voxel) metabolite levels were quantified, following manomolecule subtraction, from short-echo-time spectra (TE = 46 ms) acquired at 4.0 Tesla with localization by adiabatic selective refocusing (LASER). Nineteen metabolites were fit using a time domain Levenberg-Marquardt minimization that incorporated prior knowledge of metabolite lineshapes. The macromolecule contribution to the spectrum was reduced by 87% (P < 0.05) when the acquisition of single averages of the full spectrum and macromolecule spectrum were interleaved to reduce subtraction errors due to motion. Subtracting the Hankel Lanczos singular value decomposition (HLSVD) fit of the macromolecule spectrum, which contained no random noise, did not alter quantified metabolite levels but did not increase metabolite quantification precision. Several metabolites had higher concentrations in the posterior hippocampus compared to parietal white matter, which emphasizes the need to carefully control for partial volume contamination in hippocampal spectroscopy studies.

Paramagnetic metal agents for contrast-enhanced magnetic resonance

The transverse relaxation rate (R2 = 1/T2) of many biological tissues are altered by endogenous magnetized particles (i.e., ferritin, deoxyhemoglobin), and may be sensitive to the pathological progression of neurodegenerative disorders associated with altered brain-iron stores. R2 measurements using Carr–Purcell–Meiboom–Gill (CPMG) acquisitions are sensitive to the refocusing pulse interval (2τcp), and have been modeled as a chemical exchange (CE) process, while R2 measurements using a localization by adiabatic selective refocusing (LASER) sequence have an additional relaxation rate contribution that has been modeled as a R2ρ process. However, no direct comparison of the R2 measured using these two sequences has been described for a controlled phantom model of magnetized particles. The three main objectives of this study were: (1) to compare the accuracy of R2 relaxation rate predictions from the CE model with experimental data acquired using a conventional CPMG sequence, (2) to compare R2 estimates obtained using LASER and CPMG acquisitions, and (3) to determine whether the CE model, modified to account for R2ρ relaxation, adequately describes the R2 measured by LASER for a full range of τcp values. In all cases, our analysis was confined to spherical magnetic particles that satisfied the weak field regime. Three phantoms were produced that contained spherical magnetic particles (10 μm diameter polyamide powders) suspended in Gd-DTPA (1.0, 1.5, and 2.0 mmol/L) doped gel. Mono-exponential R2 measurements were made at 4 T as a function of refocusing pulse interval. CPMG measurements of R2 agreed with CE model predictions while significant differences in R2 estimates were observed between LASER and CPMG measurements for short τcp acquisitions. The discrepancy between R2 estimates is shown to be attributable to contrast enhancement in LASER due to T2ρ relaxation.