Stimulated Echo Acquisition Mode Sequence Research Articles

Quantification of the neurochemical profile of the human putamen using STEAM MRS in a cohort of elderly subjects at 3 T and 7 T: Ruminations on the correction strategy for the tissue voxel composition.

The aim of this work is to quantify the metabolic profile of the human putamen in vivo in a cohort of elderly subjects using single-voxel proton magnetic resonance spectroscopy. To obtain metabolite concentrations specific to the putamen, we investigated a correction method previously proposed to account for the tissue composition of the volume of interest. We compared the method with the conventional approach, which a priori assumes equal metabolite concentrations in GM and WM. Finally, we compared the concentrations acquired at 3 Tesla (T) and 7 T MRI scanners. Spectra were acquired from 15 subjects (age: 67.7 ± 8.3 years) at 3 T and 7 T, using an ultra-short echo time, stimulated echo acquisition mode sequence. To robustly estimate the WM-to-GM metabolite concentration ratio, five additional subjects were measured for whom the MRS voxel was deliberately shifted from the putamen in order to increase the covered amount of surrounding WM. The concentration and WM-to-GM concentration ratio for 16 metabolites were reliably estimated. These ratios ranged from ~0.3 for γ-aminobutyric acid to ~4 for N-acetylaspartylglutamate. The investigated correction method led to significant changes in concentrations compared to the conventional method, provided that the ratio significantly differed from unity. Finally, we demonstrated that differences in tissue voxel composition cannot fully account for the observed concentration difference between field strengths. We provide not only a fully comprehensive quantification of the neurochemical profile of the putamen in elderly subjects, but also a quantification of the WM-to-GM concentration ratio. This knowledge may serve as a basis for future studies with varying tissue voxel composition, either due to tissue atrophy, inconsistent voxel positioning or simply when pooling data from different voxel locations.

Radiological hints for differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia

Differentiation cerebellar multiple systemic atrophy (MSA-C) from spinocerebellar ataxia (SCA) is important. The “hot cross bun” sign (HCBS) at pons and magnetic resonance spectroscopy (MRS) are helpful. However, the prevalence of HCBS and the alteration of cerebellar MRS parameters are evolving with disease progression. We hypothesized that since the HCBS and MRS are evolving with time, different parameters for differentiation of MSA-C and SCA are required at different disease stages. The aim of this study was to evaluate the HCBS and MRS changes in patients with MSA-C and SCA at different disease stages. A total of 398 patients with molecularly confirmed SCA (SCA1, 2, 3, 6, 17) and 286 patients diagnosed with probable MSA-C (without mutations in SCA1, 2, 3, 6, 17 genes), who had received brain magnetic resonance imaging (MRI) and MRS from January 2000 to January 2020, were recruited. Twenty-five patients were molecularly identified as having SCA1, 68 as SCA2, 253 as SCA3, 34 as SCA6, and 18 as SCA17. We compared their clinical parameters and neuroimaging features at different disease stages. The presence of HCBS was assessed using an axial T2 fast spin-echo or FLAIR sequence. Proton MRS was recorded with voxel of interest focusing on cerebellar hemispheres and cerebellar vermis and avoiding cerebrospinal fluid spaces space using a single-voxel stimulated echo acquisition mode sequence. We found that patients with MSA-C tend to have a higher prevalence of pontine HCBS, worse Scale for the Assessment and Rating of Ataxia scores, lower cerebellar N-acetyl aspartate (NAA)/creatinine (Cr), and choline (Cho)/Cr, compared to patients with SCA at corresponding disease stages. In MSA-C patients with a disease duration < 1 year and without pontine HCBS, a cerebellar NAA/Cr ≤ 0.79 is a good indicator of the possibility of MSA-C. By using the pontine HCBS and cerebellar MRS, discerning MSA-C from SCA became possible. This study provides cutoff values of MRS to serve as clues in differentiating MSA-C from SCAs.

Reproducibility of 7-T brain spectroscopy using an ultrashort echo time STimulated Echo Acquisition Mode sequence and automated voxel repositioning.

Establishing the reproducibility of brain MRS is important for clinical studies so that researchers can evaluate changes in metabolites due to treatment or the course of a disease and better understand the brain in healthy and disordered states. Prior 7-T MRS reproducibility studies using the stimulated echo acquisition mode (STEAM) sequence have focused on the anterior cingulate cortex or posterior cingulate cortex and precuneus. The purpose of this study was to evaluate the reproducibility of metabolite measurements in the dorsolateral prefrontal cortex (DLPFC) using an ultrashort echo time (TE) STEAM sequence and automated voxel repositioning. Spectra were acquired during two scan sessions from nine subjects using the AutoAlign method for voxel repositioning. Reproducibility was evaluated with coefficients of variation (CVs) and percentage differences. The mean intrasubject CVs were less than 6% for the major metabolites glutamate, N-acetylaspartate, total creatine, total choline, and myo-inositol. The mean CVs were less than 20% for the smaller signals of GABA, glutamine, glutathione, and taurine. These results indicate that 7-T MRS using a STEAM sequence with ultrashort TE and automated voxel repositioning provides excellent reproducibility of metabolites in the DLPFC.

Bone Marrow Fat Distribution in Patients With β-Thalassemia: A Study Using Chemical Shift-Based Water-Fat MRI

Molecular studies have shown the changes in bone marrow fat in relation to altered hematopoiesis. This study aims to investigate the changes in the bone marrow fat in patients affected by β-thalassemia by using chemical shift-encoded (CSE)-MRI. Twenty-three subjects, comprising of six healthy (17-31 years old) and 17 β-thalassemia subjects (19-39 years old), were scanned using a multiecho fast low angle shot sequence (0.94 × 0.94 × 3.00 mm3) and a stimulated echo acquisition mode sequence using 3T MRI. Bone marrow proton density fat fraction (PDFF) was quantified in the left femur of each subject. Regression and Bland-Altman analysis were used to analyze agreement between CSE-MRI and 1H-MRS. PDFF distribution was analyzed using Hartigan's dip test and the computed Wasserstein distances. Jonckheere-Terpstra trend analysis was performed to evaluate the effect of disease severity on PDFF distribution. An excellent agreement was found between PDFF measured using CSE-MRI with 1H-MRS (R2 = 0.91; bias =-1.41%). Healthy subjects showed left-skewed or bimodal PDFF distribution while β-thalassemia subjects showed bimodal, normal or right-skewed distribution. Jonckheere-Terpstra test shows that PDFF distribution was increasingly different from the norm as disease severity increased (TJT = 166.0, z = 3.806, p < 0.05). Increase in variability of PDFF distribution within each subject group was also seen with increasing disease severity (TJT = 169.0, z = 3.971, p < 0.05). CSE-MRI is a promising tool to demonstrate spatial changes and variability in marrow fat distribution, resulting from ineffective erythropoiesis.

Fat Composition Measured by Proton Spectroscopy: A Breast Cancer Tumor Marker?

Altered metabolism including lipids is an emerging hallmark of breast cancer. The purpose of this study was to investigate if breast cancers exhibit different magnetic resonance spectroscopy (MRS)-based lipid composition than normal fibroglandular tissue (FGT). MRS spectra, using the stimulated echo acquisition mode sequence, were collected with a 3T scanner from patients with suspicious lesions and contralateral normal tissue. Fat peaks at 1.3 + 1.6 ppm (L13 + L16), 2.1 + 2.3 ppm (L21 + L23), 2.8 ppm (L28), 4.1 + 4.3 ppm (L41 + L43), and 5.2 + 5.3 ppm (L52 + L53) were quantified using LCModel software. The saturation index (SI), number of double bods (NBD), mono and polyunsaturated fatty acids (MUFA and PUFA), and mean chain length (MCL) were also computed. Results showed that mean concentrations of all lipid metabolites and PUFA were significantly lower in tumors compared with that of normal FGT (p ≤ 0.002 and 0.04, respectively). The measure best separating normal and tumor tissues after adjusting with multivariable analysis was L21 + L23, which yielded an area under the curve of 0.87 (95% CI: 0.75–0.98). Similar results were obtained between HER2 positive versus HER2 negative tumors. Hence, MRS-based lipid measurements may serve as independent variables in a multivariate approach to increase the specificity of breast cancer characterization.

Comparison of PGSE and STEAM DTI acquisitions with varying diffusion times for probing anisotropic structures in human kidneys.

To evaluate the sensitivity of stimulated-echo acquisition mode (STEAM) and pulsed-gradient spin-echo (PGSE) diffusion tensor imaging (DTI) acquisitions with different diffusion times for measuring renal tissue anisotropy. Twelve healthy volunteers underwent an MRI examination at a 3T scanner including STEAM and PGSE DTI with variable diffusion times Δ (20.3, 37 and 125ms). Three volunteers were scanned twice to test the reproducibility for repeated examinations. Diffusion parameters fractional anisotropy (FA) and apparent diffusion coefficient (ADC) in the automatically segmented cortical and medullary regions of interests in both kidneys were calculated and averaged over all subjects for further analysis. Moreover, 5-grade qualitative evaluation of the FA and ADC maps from each sequence was conducted by two experienced radiologists in a consensus. The cortex-medulla difference in the STEAM sequence was significantly higher than that in PGSE with short ∆=20.3ms (P<0.001) and in PGSE with intermediate ∆=37ms (P<0.05) diffusion times. Reproducibility of the FA/ADC measurements was very good and comparable for all acquisition modes investigated. For the FA maps, the PGSE sequence with intermediate diffusion time scored highest in the subjective visual assessment of radiologists. The delineation of anisotropy in renal tissue is depending on the used diffusion time of the DTI sequence. A PGSE acquisition at a diffusion time of about 37ms provides reproducible results with optimal corticomedullary contrast in FA and ADC maps and good image quality.

Motion and eddy current-induced signal dephasing in in vivo cardiac DTI.

To address motion in cardiac DWI, stimulated-echo acquisition mode (STEAM) and second-order motion-compensated spin-echo (SE) sequences have been proposed. Despite applying motion-compensation strategies, residual motion can cause misleading signal attenuation. The purpose of this study is to estimate the motion-induced error in both sequences by analysis of image phase. Diffusion-weighted motion-compensated SE sequences and STEAM imaging was applied in vivo with diffusion encoding along 3 orthogonal directions. A b-value range of 100 to 600 s/mm2 and trigger delays of 25%, 50%, and 75% of end systole and middiastole were used. Eddy-current contributions were obtained from phantom measurements. After computation of motion-induced phase maps, the amount of signal dephasing was computed from phase gradients, and the resulting errors in diffusion tensor parameters were calculated. Motion-induced dephasing from the STEAM sequence showed less dependency on the b-value and no dependency on the heart phase, whereas SE imaging performed best at 75% end systole followed by 50% end systole and middiastole. For a typical experimental setting, errors of 3.3%/3.0% mean diffusivity, 4.9%/4.8% fractional anisotropy, 2.9º/3.2º helix angulation, 0.8º/0.7º transverse angulation, and 9.9º/10.0º sheet angulation (SE/STEAM) were calculated. Image phase contains valuable information regarding uncompensated motion and eddy currents in cardiac DTI. Although the trigger delay window for SE is narrower compared with the STEAM-based approach, imaging in both systole and diastole is feasible and both sequences perform similarly if the trigger delays are selected carefully with SE.

Novel insights into in-vivo diffusion tensor cardiovascular magnetic resonance using computational modeling and a histology-based virtual microstructure.

PurposeTo develop histology‐informed simulations of diffusion tensor cardiovascular magnetic resonance (DT‐CMR) for typical in‐vivo pulse sequences and determine their sensitivity to changes in extra‐cellular space (ECS) and other microstructural parameters.MethodsWe synthesised the DT‐CMR signal from Monte Carlo random walk simulations. The virtual tissue was based on porcine histology. The cells were thickened and then shrunk to modify ECS. We also created idealised geometries using cuboids in regular arrangement, matching the extra‐cellular volume fraction (ECV) of 16–40%. The simulated voxel size was 2.8 × 2.8 × 8.0 mm3 for pulse sequences covering short and long diffusion times: Stejskal–Tanner pulsed‐gradient spin echo, second‐order motion‐compensated spin echo, and stimulated echo acquisition mode (STEAM), with clinically available gradient strengths.ResultsThe primary diffusion tensor eigenvalue increases linearly with ECV at a similar rate for all simulated geometries. Mean diffusivity (MD) varies linearly, too, but is higher for the substrates with more uniformly distributed ECS. Fractional anisotropy (FA) for the histology‐based geometry is higher than the idealised geometry with low sensitivity to ECV, except for the long mixing time of the STEAM sequence. Varying the intra‐cellular diffusivity (D IC) results in large changes of MD and FA. Varying extra‐cellular diffusivity or using stronger gradients has minor effects on FA. Uncertainties of the primary eigenvector orientation are reduced using STEAM.ConclusionsWe found that the distribution of ECS has a measurable impact on DT‐CMR parameters. The observed sensitivity of MD and FA to ECV and D IC has potentially interesting applications for interpreting in‐vivo DT‐CMR parameters.

Long TE STEAM and PRESS for estimating fat olefinic/methyl ratios and relative ω-3 fat content at 3T.

Fat olefinic/methyl ratios provide a measure of fat unsaturation. The methyl resonance linewidth is altered with the presence of ω-3 fat. To optimize stimulated echo acquisition mode (STEAM) and point resolved spectroscopy (PRESS) echo times (TE) at 3T to 1) improve olefinic/methyl ratios and 2) enable relative ω-3 fat content assessment. Technical development on phantoms and healthy volunteers. Nine edible oils and four healthy volunteers (tibial bone marrow). STEAM (mixing time = 20 msec) and PRESS sequences at 3T. High-resolution oil spectra at 16.5T. 3T STEAM and PRESS olefinic/methyl ratios as a function of TE were compared to 16.5T measures for the oils, and to a literature-deduced value for tibial bone marrow. Oil methyl linewidths were calculated at each TE to investigate correlation with expected ω-3 fatty acid content. Percent differences were calculated between oil olefinic/methyl ratios obtained at 3T and 16.5T. Linear regression R2 values measured correlation of methyl linewidth to ω-3 content. STEAM, TE = 120 msec, resulted in average oil olefinic/methyl ratios that differ by about -4.8% compared to high-resolution ratios. Tibial bone marrow olefinic/methyl ratios differ by -1.8% compared with literature-obtained ratios. PRESS, TE = 180 msec, resulted in oil ratios that differ by 7.8% and tibial bone marrow ratios that differ by 0.2%. A TE of 160 msec for both STEAM and PRESS enabled relative levels of oil ω-3 fatty acid content to be estimated (R2 values ≥0.9). STEAM, TE = 120 msec (mixing time = 20 msec), and PRESS, TE = 180 msec, optimally estimated olefinic/methyl ratios. STEAM and PRESS, TE = 160 msec, enable relative oil ω-3 fatty acid estimation from methyl linewidths. 1 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017.

An efficient fat suppression technique for stimulated-echo based CMR

Background Stimulated-echo acquisition mode (STEAM) is one of the key pulse sequences in CMR imaging, as it alleviates rapid magnetization decay with T2 relaxation. Fat suppression is frequently implemented in cardiac imaging to improve visualization and tissue characterization, albeit at the cost of reduced temporal resolution and signal-to-noise ratio (SNR), as well as possible increase of specific absorption rate (SAR). The purpose of this work is to develop an efficient fat suppression method (Spectrally-Presaturated Modulation (SPM)) for STEAM sequences to enable imaging at high temporal-resolution, with high SNR, and no increase in scan time. Methods The developed method is based on saturating the fat magnetization prior to applying the STEAM modulation; therefore, only the water-content of the tissues is modulated by the sequence, resulting in fat-suppressed images without the need to run the fat suppression module during image acquisition (Figure 1). The potential significance of the proposed method has been tested in two STEAM-based cardiac MRI applications: complementary spatial-modulation of magnetization (CSPAMM) tagging, and black-blood cine imaging. In vivo experiments were conducted to evaluate the developed technique and compare it to the commonly implemented chemical-shift selective (CHESS)

High angular resolution diffusion imaging with stimulated echoes: compensation and correction in experiment design and analysis.

Stimulated echo acquisition mode (STEAM) diffusion MRI can be advantageous over pulsed-gradient spin-echo (PGSE) for diffusion times that are long compared with T2. It therefore has potential for biomedical diffusion imaging applications at 7T and above where T2 is short. However, gradient pulses other than the diffusion gradients in the STEAM sequence contribute much greater diffusion weighting than in PGSE and lead to a disrupted experimental design. Here, we introduce a simple compensation to the STEAM acquisition that avoids the orientational bias and disrupted experiment design that these gradient pulses can otherwise produce. The compensation is simple to implement by adjusting the gradient vectors in the diffusion pulses of the STEAM sequence, so that the net effective gradient vector including contributions from diffusion and other gradient pulses is as the experiment intends. High angular resolution diffusion imaging (HARDI) data were acquired with and without the proposed compensation. The data were processed to derive standard diffusion tensor imaging (DTI) maps, which highlight the need for the compensation. Ignoring the other gradient pulses, a bias in DTI parameters from STEAM acquisition is found, due both to confounds in the analysis and the experiment design. Retrospectively correcting the analysis with a calculation of the full B matrix can partly correct for these confounds, but an acquisition that is compensated as proposed is needed to remove the effect entirely.

Comparison of optimized long echo time STEAM and PRESS proton MR spectroscopy of lipid olefinic protons at 3 Tesla

To investigate the response of lipid olefinic protons (≈ 5.35 ppm) as a function of STEAM (Stimulated Echo Acquisition Mode) mixing time (TM), and echo time (TE), to find values that resolve the olefinic resonance from water in vivo while retaining sufficient olefinic signal. PRESS (Point RESolved Spectroscopy) and STEAM experiments with varying timing parameters (TE and also TM for STEAM) were conducted on nine oils (almond, canola, cod liver, corn, linseed, peanut, sesame, sunflower, and walnut oil), and on vertebral bone marrow in vivo at 3 Tesla (T). Olefinic and methylene (methyl + methylene in vivo) peak areas were measured. Optimal STEAM parameters were found to be TM = 20 ms and TE = 100 ms. The STEAM olefinic/methylene area ratios (ranging between 0.1 and 0.4) calculated for each oil correlated well with ratios deduced from oil compositions in the literature (R(2) = 0.975). The optimized STEAM sequence resolved the olefinic peak from water in vivo and yielded on average 1.91 times more olefinic signal compared with a previously optimized PRESS (TE = 200 ms) sequence tailored for the same purpose. Olefinic/(methyl + methylene) area ratios obtained with optimized STEAM and PRESS in vivo were linearly correlated (R(2) = 0.972). A STEAM sequence with TE = 100 ms and TM = 20 ms provides an alternative to the previously optimized PRESS (TE = 200 ms) sequence for determining relative amounts of lipid unsaturation at 3T.

Reproducibility of phase rotation STEAM at 3T: Focus on glutathione

The purpose of this study was to determine the reproducibility of a very short echo time (TE) phase rotation stimulated echo acquisition mode (STEAM) sequence at 3T with a focus on the detection of glutathione. Ten healthy subjects were scanned on two separate visits. Spectra were acquired from voxels placed in the anterior and posterior cingulates. Reproducibility was assessed using mean coefficients of variation (CVs) and mean absolute differences (ADs), and reliability was assessed using standard error of measurement (SEM) and intraclass correlations (ICCs). Phantoms containing glutathione and metabolites with overlapping resonances were scanned to test the validity of glutathione quantification. Excellent reproducibility as illustrated by CVs ≤8.3% and ADs ≤11.6% for both regions was obtained for glutathione and other commonly reported metabolites. Reproducibility measures for γ-aminobutyric acid and glutamine were good overall with CVs ranging from 6.4%-10.5% and ADs ranging from 8.6%-15.5% for both regions. Glutathione absolute and relative reliability were very good (SEMs ≤9.9%) and fair (ICCs = 0.42-0.51), respectively. Phantom studies demonstrated the ability to accurately detect glutathione from other metabolites with overlapping resonances with great precision (R(2) = 0.99). A very short TE phase rotation STEAM sequence proved reproducible for metabolites difficult to quantify but important for the study of psychiatric and neurological illness.

Functional diffusion‐weighted magnetic resonance spectroscopy of the human primary visual cortex at 7 T

Microstructural and metabolic changes directly related to neuronal activation have been investigated using functional diffusion-weighted spectroscopy. The volume of interest was positioned in the primary visual cortex. A time series of alternating diffusion- and non-diffusion-weighted (1)H spectra was acquired at 7 T employing stimulated echo acquisition mode sequence and a long diffusion time (Δ = 245 ms). Time-resolved series of metabolite apparent diffusion coefficient values were derived. Significant increases in apparent diffusion coefficient of 3.3 ± 1.4% (p = 0.05) and 3.9 ± 0.9% (p = 0.002) for total n-acetyl aspartate and total creatine, respectively, and 8.1 ± 2.5% (p = 0.03) for total choline were observed in response to visual stimulation. The increase in apparent diffusion coefficient for these metabolites is a potential indication for microstructural changes in neurons during neural activation and/or for an increase in the energy-dependent cytoplasmic streaming associated with enhanced metabolism during visual stimulation.

Use of in vivo bioluminescence and MRI to determine hyperthermia-induced changes in luciferase activity under the control of an hsp70 promoter

We investigated the in vivo effect of hyperthermia on the expression of heat shock proteins and MRI changes in three tumor cell lines. Three tumor cell lines (SCCVII, NIH3T3, M21) were transfected with a plasmid containing the heat shock protein 70 gene (hsp70) promoter fragment and the luciferase reporter gene, and injected into mice. Tumors of 1100 mm³ in size were exposed to five different temperatures (38, 40, 42, 44 and 46 °C) in a water bath. Bioluminescence and MRI were performed at set time intervals. The MRI scan protocol was as follows: T₁-weighted spin echo ± contrast medium, T₂-weighted fast spin echo, dynamic contrast-enhanced MRI, diffusion-weighted stimulated echo acquisition mode sequence, T₂ time obtained on a 1.5T General Electric MRI scanner. Immunoblotting was also performed. hsp70 transcription was strongly induced at 42 and 44 °C, reaching values as high as 8531.5 ± 432.1-fold above baseline in NIH3T3 tumors. At these temperatures, significant increases in the uptake of contrast medium, slope of initial enhancement, Ak(ep) values and apparent diffusion coefficient (ADC) were observed in the 8-h scan of the NIH3T3 cell line. In SCCVII tumors, ADC increased by about 23% (p = 0.010) in the scans performed at 8, 24, 48 and 96 h. At 46 °C, luciferase activity was reduced significantly in the three cell lines. In all tumor types, a significant increase in ADC was observed, which was highest in SCCVII tumors (33.8%; p < 0.01). In accordance with the bioluminescence results, significant Hsp70 protein production was shown by immunoblot analysis. The best correlation coefficient between luciferase activity and immunoblotting results was found for M21 tumors (r = 0.93, p < 0.0001). Different tissue types display distinct patterns of hsp70 transcription. MRI can be used, in combination with optical imaging, to provide information on hsp70 transcription and protein production. The major finding of the present study was that heat-related biochemical changes in tumor tissue can be determined by MRI.

Reproducibility of MRI‐determined proton density fat fraction across two different MR scanner platforms

To evaluate magnetic resonance imaging (MRI)-determined proton density fat fraction (PDFF) reproducibility across two MR scanner platforms and, using MR spectroscopy (MRS)-determined PDFF as reference standard, to confirm MRI-determined PDFF estimation accuracy. This prospective, cross-sectional, crossover, observational pilot study was approved by an Institutional Review Board. Twenty-one subjects gave written informed consent and underwent liver MRI and MRS at both 1.5T (Siemens Symphony scanner) and 3T (GE Signa Excite HD scanner). MRI-determined PDFF was estimated using an axial 2D spoiled gradient-recalled echo sequence with low flip-angle to minimize T1 bias and six echo-times to permit correction of T2* and fat-water signal interference effects. MRS-determined PDFF was estimated using a stimulated-echo acquisition mode sequence with long repetition time to minimize T1 bias and five echo times to permit T2 correction. Interscanner reproducibility of MRI determined PDFF was assessed by correlation analysis; accuracy was assessed separately at each field strength by linear regression analysis using MRS-determined PDFF as reference standard. 1.5T and 3T MRI-determined PDFF estimates were highly correlated (r = 0.992). MRI-determined PDFF estimates were accurate at both 1.5T (regression slope/intercept = 0.958/-0.48) and 3T (slope/intercept = 1.020/0.925) against the MRS-determined PDFF reference. MRI-determined PDFF estimation is reproducible and, using MRS-determined PDFF as reference standard, accurate across two MR scanner platforms at 1.5T and 3T.

Improvements in high‐field localized MRS of the medial temporal lobe in humans using new deformable high‐dielectric materials

The intrinsic nonuniformities in the transmit radiofrequency field from standard quadrature volume resonators at high field are particularly problematic for localized MRS in areas such as the temporal lobe, where a low signal-to-noise ratio and poor metabolite quantification result from destructive B₁⁺ field interference, in addition to line broadening and signal loss from strong susceptibility gradients. MRS of the temporal lobe has been performed in a number of neurodegenerative diseases at clinical fields, but a relatively low signal-to-noise ratio has prevented the reliable quantification of, for example, glutamate and glutamine, which are thought to play a key role in disease progression. Using a recently developed high-dielectric-constant material placed around the head, localized MRS of the medial temporal lobe using the stimulated echo acquisition mode sequence was acquired at 7 T. The presence of the material increased the signal-to-noise ratio of MRS by a factor of two without significantly reducing the sensitivity in other areas of the brain, as shown by the measured B₁⁺ maps. An increase in the receive sensitivity B₁⁻ was also measured close to the pads. The spectral linewidth of the unsuppressed water peak within the voxel of interest was reduced slightly by the introduction of the dielectric pads (although not to a statistically significant degree), a result confirmed by using a pad composed of lipid. Using LCmodel for quantitative analysis of metabolite concentrations, the increase in signal-to-noise ratio and the slight decrease in spectral linewidth contributed to statistically significant reductions in the Cramer-Rao lower bounds (CRLBs), also allowing the levels of glutamate and glutamine to be quantified with CRLBs below 20%.

Early detection of radiation therapy response in non-Hodgkin's lymphoma xenografts by in vivo 1H magnetic resonance spectroscopy and imaging.

The purpose of the study was to investigate the capability of (1)H MRS and MRI methods for detecting early response to radiation therapy in non-Hodgkin's lymphoma (NHL). Studies were performed on the WSU-DLCL2 xenograft model in nude mice of human diffuse large B-cell lymphoma, the most common form of NHL. Radiation treatment was applied as a single 15 Gy dose to the tumor. Tumor lactate, lipids, total choline, T(2) and apparent diffusion coefficients (ADC) were measured before treatment and at 24 h and 72 h after radiation. A Hadamard-encoded slice-selective multiple quantum coherence spectroscopy sequence was used for detecting lactate (Lac) while a stimulated echo acquisition mode sequence was used for detection of total choline (tCho) and lipids. T(2)- and diffusion-weighted imaging sequences were used for measuring T(2) and ADC. Within 24 h after radiation, significant changes were observed in the normalized integrated resonance intensities of Lac and the methylenes of lipids. Lac/H(2)O decreased by 38 +/- 15% (p = 0.03), and lipid (1.3 ppm, CH(2))/H(2)O increased by 57 +/- 14% (p = 0.01). At 72 h after radiation, tCho/H(2)O decreased by 45 +/- 14% (p = 0.01), and lipid (2.8 ppm, polyunsaturated fatty acid)/H(2)O increased by 970 +/- 36% (p = 0.001). ADC increased by 14 +/- 2% (p = 0.003), and T(2) did not change significantly. Tumor growth delay and regression were observed thereafter. This study enabled comparison of the relative sensitivities of various (1)H MRS and MRI indices to radiation and suggests that (1)H MRS/MRI measurements detect early responses to radiation that precede tumor volume changes.

In vivo (1)H MRS of WSU-DLCL2 human non-Hodgkin's lymphoma xenografts: response to rituximab and rituximab plus CHOP.

In order to identify early (1)H MRS metabolic markers of response to rituximab immunotherapy and to rituximab plus CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine, and prednisone) combination therapy, we performed an in vivo MRS investigation of a non-Hodgkin's lymphoma (NHL) xenograft model. Human WSU-DLCL2 NHL cells were subcutaneously implanted into flanks of female severe combined immunodeficient mice. When tumor volumes reached approximately 600 mm(3), rituximab was administered for three weekly cycles at a dose of 25 mg/kg per cycle with or without CHOP. Before and after treatment, tumor lactate (Lac) and total choline (tCho) were detected using the selective multiple quantum coherence sequence and the stimulated echo acquisition mode sequence, respectively. Rituximab produced a small tumor growth delay ( approximately 5 days), whereas treatment with rituximab plus CHOP (RCHOP) led to approximately 20% tumor regression after three cycles of therapy. After one cycle of rituximab, the tCho/H(2)O ratio had decreased significantly (5%, P = 0.003), whereas the Lac/H(2)O ratio had not changed (P = 0.58). Both Lac/H(2)O and tCho/H(2)O had decreased after one cycle of RCHOP treatment (26%, P = 0.001; 10%, P = 0.016, respectively). After two cycles of RCHOP, Ki67 assay of histological tumor specimens indicated approximately 40% decrease in proliferation (P < 0.001) in the RCHOP-treated tumors; no change was detected after treatment with rituximab alone. This study suggests that decreases in tCho/H(2)O are more sensitive indices of response to rituximab, whereas decreases in Lac/H(2)O are more sensitive to response to CHOP combination therapy.

Composition of adipose tissue and marrow fat in humans by 1H NMR at 7 Tesla

Proton NMR spectroscopy at 7 Tesla (7T) was evaluated as a new method to quantify human fat composition noninvasively. In validation experiments, the composition of a known mixture of triolein, tristearin, and trilinolein agreed well with measurements by 1H NMR spectroscopy. Triglycerides in calf subcutaneous tissue and tibial bone marrow were examined in 20 healthy subjects by 1H spectroscopy. Ten well-resolved proton resonances from triglycerides were detected using stimulated echo acquisition mode sequence and small voxel (∼0.1 ml), and T1 and T2 were measured. Triglyceride composition was not different between calf subcutaneous adipose tissue and tibial marrow for a given subject, and its variation among subjects, as a result of diet and genetic differences, fell in a narrow range. After correction for differential relaxation effects, the marrow fat composition was 29.1 ± 3.5% saturated, 46.4 ± 4.8% monounsaturated, and 24.5 ± 3.1% diunsaturated, compared with adipose fat composition, 27.1 ± 4.2% saturated, 49.6 ± 5.7% monounsaturated, and 23.4 ± 3.9% diunsaturated. Proton spectroscopy at 7T offers a simple, fast, noninvasive, and painless method for obtaining detailed information about lipid composition in humans, and the sensitivity and resolution of the method may facilitate longitudinal monitoring of changes in lipid composition in response to diet, exercise, and disease.