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The purpose of this study was to evaluate the association of specific threshold values for changes in metabolic metrics measured from 1H magnetic resonance spectroscopic imaging (MRSI) to survival of patients with high-grade glioma treated with multimodality therapy.Forty-four patients with newly diagnosed high-grade glioma were prospectively enrolled. Serial MRI and MRSI scans provided measures of tumor choline, creatine, and N-acetylaspartate (NAA). Cox regression analyses adjusted for patient age, KPS, and delivery of concurrent chemotherapy were used to assess the association of changes in metabolic metrics with survival.Median follow-up time for patients at risk was 13.4 years. Overall survival (OS) was longer in patients with ≤20% increase (vs.20%) in normalized choline (p=0.024) or choline/NAA (p=0.024) from baseline to week 4 of RT. During this period, progression-free survival (PFS) was longer in patients with ≤40% increase (vs.40%) in normalized choline (p=0.013). Changes in normalized creatine, choline/creatine, and NAA/creatine from baseline to mid-RT were not associated with OS. From baseline to post-RT, changes in metabolic metrics were not associated with OS or PFS.Threshold values for serial changes in choline metrics on mid-RT MRSI associated with OS and PFS were identified. Metabolic metrics at post-RT did not predict for these survival endpoints. These findings suggest a potential clinical role for MRSI to provide an early assessment of treatment response and could enable risk-adapted therapy in clinical trial development and clinical practice.

Fat unsaturation and poly-unsaturation measures can be obtained in vivo with magnetic resonance spectroscopy (MRS) through the olefinic (≈5.4 ppm) and diallylic (≈2.8 ppm) resonances, respectively. Long echo time (TE) MRS sequences have been previously optimized for olefinic/methylene (≈1.3 ppm) or olefinic/methyl (≈0.9 ppm) measures. The objectives of this work, using a Point RESolved Spectroscopy (PRESS), are to: 1) Investigate olefinic, methyl and methylene resonance decay in subcutaneous, tibial, and breast adipose tissue to determine if a direct comparison of unsaturation measures can be made without correction for T2 losses. 2) Assess intra-individual fat unsaturation and poly-unsaturation measures in the three adipose tissues. 3) Estimate correction factors for olefinic to methylene ratios to compensate for J-coupling and T2 relaxation losses that take place when increasing PRESS TE from 40 ms to 200 ms (previously optimized long-TE). 4) Investigate the utility of an inversion recovery for resolving the olefinic resonance from water in adipose tissue. PRESS spectra were acquired from the three adipose regions (breast in female only) in healthy volunteers at 3 T. It was found that olefinic and methyl signal decays faster in breast tissue compared to in tibial bone marrow. Poly-unsaturation measures (diallylic/methylene) differ for tibial bone marrow compared to subcutaneous and breast adipose tissue, with average values of 1.7 ± 0.4, 2.2 ± 0.4, and 2.3 ± 0.8%, respectively. PRESS (TE = 40 ms) with an inversion recovery resolves the olefinic and water resonances in breast tissue with a signal to noise ratio approximately six times greater than that using PRESS with a TE of 200 ms. Stimulated Echo Acquisition Mode (STEAM) with a TE of 20 ms (mixing time of 20 ms) was also combined with IR to resolve the olefinic resonance from that of water is spinal bone marrow.

It has been previously shown that the MRS sequence stimulated echo acquisition mode (STEAM; mixing time, TM = 20 ms) with an echo time (TE) of 100 ms resolves triglyceride glycerol resonances from that of water at 3 T. The purpose of this work is to determine if STEAM with a TE of 100 ms facilitates relative quantification of diglyceride/triglyceride levels at 3 T. Spectra were obtained from tricaprylin (triglyceride) and dicaprylin (diglyceride) with a range of STEAM TE values (TM = 20 ms). TE values that resulted in two resolved glycerol resonances for triglycerides (rendering them suitable for distinguishing triglyceride contributions from those of diglycerides) were selected. One resonance resides in the 3.85-4.2 ppm spectral range (overlapping the 1,3-diglyceride resonance) and the other in the 4.2-4.6 ppm spectral range (overlapping one of the 1,2-diglyceride resonances). STEAM with TE values of 40 ms and 100 ms (TM = 20 ms) yielded two resolvable triglyceride resonances (tricaprylin phantom), at about 4 ppm and 4.4 ppm. Direct integration of the resonances showed that the former peak has 0.86 and 0.17 times the area of the latter for TE = 40 ms and 100 ms, respectively. Spectra obtained from the phantoms containing mixtures of diglyceride (1,3-dicaprylin) and triglyceride (tricaprylin) were acquired. The triglyceride contribution to the 4 ppm glycerol resonance, a mixture of signal from 1,3-diglyceride and triglyceride, can be approximated from the area of the 4.4 ppm peak, resulting in an estimate of the 1,3-diglyceride contribution. Analysis was performed for STEAM TE = 40 ms and TE = 100 ms spectra acquired from phantoms with 1,3-dicaprylin/tricaprylin weight/weight contents of 2.5%/97.5%, 5%/95%, 10%/90% and 20%/80%. Concentration ratios of 1,3-dicaprylin/tricaprylin estimated with both STEAM TE values resulted in linear correlations with expected concentration ratios (R

Tissue omega-3 (ω-3) content is biologically important to disease; however, its quantification with magnetic resonance spectroscopy in vivo is challenging due to its low concentration. In addition, the ω-3 methyl resonance (≈ 0.98 ppm) overlaps that of the non-ω-3 (≈ 0.90 ppm), even at 9.4 T. We demonstrate that a Point-RESolved Spectroscopy (PRESS) sequence with an echo time (TE) of 109 ms resolves the ω-3 and non-ω-3 methyl peaks at 9.4 T. Sequence efficacy was verified on five oils with differing ω-3 fat content; the ω-3 content obtained correlated with that measured using 16.5 T NMR (R2 = 0.97). The PRESS sequence was also applied to measure ω-3 content in visceral adipose tissue of three different groups (all n = 3) of mice, each of which were fed a different 20% w/w fat diet. The fat portion of the diet consisted of low (1.4%), medium (9.0%) or high (16.4%) ω-3 fat. The sequence was also applied to a control mouse fed a standard chow diet (5.6% w/w fat, which was 5.9% ω-3). Gas chromatography (GC) analysis of excised tissue was performed for each mouse. The ω-3 fat content obtained with the PRESS sequence correlated with the GC measures (R2 = 0.96). Apparent T2 times of methyl protons were assessed by obtaining spectra from the oils and another group of four mice (fed the high ω-3 diet) with TE values of 109 and 399 ms. Peak areas were fit to a mono-exponentially decaying function and the apparent T2 values of the ω-3 and non-ω-3 methyl protons were 906 ± 148 and 398 ± 78 ms, respectively, in the oils. In mice, the values were 410 ± 68 and 283 ± 57 ms for ω-3 and non-ω-3 fats, respectively.

Background Fat olefinic/methyl ratios provide a measure of fat unsaturation. The methyl resonance linewidth is altered with the presence of ω-3 fat. Purpose 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. Study type Technical development on phantoms and healthy volunteers. Population Nine edible oils and four healthy volunteers (tibial bone marrow). Field strength/sequence STEAM (mixing time = 20 msec) and PRESS sequences at 3T. High-resolution oil spectra at 16.5T. Assessment 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. Statistical tests 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. Results 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). Data conclusion 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. Level of evidence 1 Technical Efficacy Stage 1 J. Magn. Reson. Imaging 2017.

MRS of 13 C4 -labelled glutamate (13 C4 -Glu) during an infusion of a carbon-13 (13 C)-labelled substrate, such as uniformly labelled glucose ([U-13 C6 ]-Glc), provides a measure of Glc metabolism. The presented work provides a single-shot indirect 13 C detection technique to quantify the approximately 2.51 ppm 13 C4 -Glu satellite proton (1 H) peak at 9.4 T. The methodology is an optimized point-resolved spectroscopy (PRESS) sequence that minimizes signal contamination from the strongly coupled protons of N-acetylaspartate (NAA), which resonate at approximately 2.49 ppm. J-coupling evolution of protons was characterized numerically and verified experimentally. A (TE1 , TE2 ) combination of (20 ms, 106 ms) was found to be suitable for minimizing NAA signal in the 2.51 ppm 1 H 13 C4 -Glu spectral region, while retaining the 13 C4 -Glu 1 H satellite peak. The efficacy of the technique was verified on phantom solutions and on two rat brains in vivo during an infusion of [U-13 C6 ]-Glc. LCModel was employed for analysis of the in vivo spectra to quantify the 2.51 ppm 1 H 13 C4 -Glu signal to obtain Glu C4 fractional enrichment time courses during the infusions. Cramer-Rao lower bounds of about 8% were obtained for the 2.51 ppm 13 C4 -Glu 1 H satellite peak with the optimal TE combination.

Point-resolved spectroscopy (PRESS), characterized by two TEs (TE1 and TE2 ), can be employed to perform animal magnetic resonance spectroscopy (MRS) studies at 9.4 T. Taurine (Tau) and choline (Cho) are relevant metabolites that can be measured by MRS. In this work, the response of the J-coupled protons of Tau as a function of PRESS TE1 and TE2 was characterized at 9.4 T to achieve two objectives. The first was to determine two TE1 and TE2 combinations that could be used to obtain T2 -corrected measures of Tau (3.42 ppm) that were minimally influenced by J coupling. The second was to exploit the Tau J coupling to find a timing combination that minimized the 3.25-ppm Tau signal to enable the Cho (3.22 ppm) resonance to be resolved from the overlapping Tau signal. The response of Tau protons was investigated both numerically and experimentally. It was numerically determined that the timings {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms, 70 ms} yielded similar 3.42-ppm Tau resonance areas (5% difference), rendering them suitable for Tau T2 determination. {TE1 , TE2 } = {25 ms, 50 ms} was found to yield minimal 3.25-ppm Tau signal, reducing its interference with Cho. The efficacy of the timings was demonstrated on phantom solutions and in vivo in four Sprague Dawley rats. LCModel was employed to analyse the in vivo spectra and Tau T2 values were estimated by fitting the Tau peak areas obtained with {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms, 70 ms} to a monoexponentially decaying function. An average Tau T2 of 106 ms (standard deviation, 12 ms) was obtained. LCModel analysis of rat spectra obtained with {TE1 , TE2 } = {25 ms, 50 ms} demonstrated negligible levels of Tau signal, compared with that obtained with short TE.

BACKGROUND The purpose of this study was to evaluate the association of specific threshold values for changes in metabolic metrics measured from 1H magnetic resonance spectroscopic imaging (MRSI) to survival of patients with high-grade glioma treated with multimodality therapy. METHODS Forty-four patients with newly diagnosed high-grade glioma were prospectively enrolled. Serial MRI and MRS scans were performed at baseline, week 4 of radiation therapy (RT), and two months post-RT to measure tumor choline, creatine, and N-acetylaspartate (NAA) normalized to contralateral normal brain. Serial changes in metabolites were assessed using the Wilcoxon signed-rank test. Cox regression analyses adjusted for patient age, KPS, and delivery of concurrent chemotherapy were used to assess the association of changes in metabolic metrics with survival. RESULTS Median follow-up time was 13.4 years, and vital status was available for 95.1% of patients. Mean normalized choline, creatine and choline/creatine decreased significantly after baseline to post-RT in the overall group of patients (all P < 05). Overall survival (OS) was longer in patients with ≤ 20% increase (vs. > 20%) in normalized choline (P = .024) or choline/NAA (P = .024) from baseline to week 4 of RT. During this period, progression-free survival (PFS) was longer in with patients ≤ 40% increase (vs. > 40%) in normalized choline (P = .013). From mid-RT to post-RT, ≤ 40% decrease (vs. > 40%) in normalized choline/NAA (P < .001) or choline/creatine (P = .014), or ≤ 40% increase (vs. > 40%) in NAA/creatine (P = .030) were associated with reduced median OS. CONCLUSIONS Threshold values for serial changes in choline metrics on MRSI associated with OS and PFS were identified. These findings suggest a potential clinical role for MRSI to provide an early assessment of treatment response, and could enable risk-adapted therapy in clinical trial development and clinical practice.

MRS of

The glycerol methylene proton resonances (4-4.5 parts per million, ppm), which arise from the triglyceride backbone, are relevant to fat composition assessment and can be measured with proton MRS. The purpose of the presented work is to determine long TE (echo time) point resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) values at 3 T to resolve the glycerol resonances from that of overlapping water. The response of the glycerol methylene protons of nine edible oils as a function of PRESS and STEAM TE (mixing time, TM = 20 ms) was investigated. In addition, high resolution NMR spectra of the oils were acquired at 16.5 T. Long TE values where J-coupling losses were lowest were selected, namely a TE of 180 ms for PRESS (first echo time 17 ms) and a TE of 100 ms for STEAM (mixing time 20 ms). Oil olefinic (≈5.4 ppm) to glycerol ratios were calculated from the long TE spectra and correlated with 16.5 T ratios. The two techniques yielded olefinic/glycerol ratios that correlated with 16.5 T ratios (R

The purpose of this work was to investigate the effect of J-coupling interactions on the quantification and T2 determination of 1.3-ppm lipid methylene protons at 3 T. The response of the 1.3-ppm protons of hexanoic, heptanoic, octanoic, linoleic and oleic acid was measured as a function of point-resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) TE. In addition, a narrow-bandwidth refocusing PRESS sequence designed to rewind J-coupling evolution of the 1.3-ppm protons was applied to the five fatty acids, to corn oil and to tibial bone marrow of six healthy volunteers. Peak areas were plotted as a function of TE, and data were fitted to monoexponentially decaying functions to determine Mo (the extrapolated area for TE = 0 ms) and T2 values. In phantoms, rewinding J-coupling evolution resulted in 198%, 64%, 44%, 20% and 15% higher T2 values for heptanoic, octanoic, linoleic and oleic acid, and corn oil, respectively, compared with those obtained with standard PRESS. The narrow-bandwidth PRESS sequence also resulted in significant changes in Mo , namely -77%, -22%, 28%, 23% and 28% for heptanoic, octanoic, linoleic and oleic acid, and corn oil, respectively. T2 values obtained with STEAM were closer to the values measured with narrow-bandwidth PRESS. On average, in tibial bone marrow (six volunteers) rewinding J-coupling evolution resulted in 21% ± 3% and 9 % ± 1% higher Mo and T2 values, respectively. This work demonstrates that the consequence of neglecting to consider scalar coupling effects on the quantification of 1.3-ppm lipid methylene protons and their T2 values is not negligible. The linoleic and oleic acid T2 results indicate that T2 measures of lipids with standard MRS techniques are dependent on lipid composition.

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 RSTEAM, 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 (RSTEAM, 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.

9.4T 1H magnetic resonance spectroscopy (MRS) was utilized to track the response of mouse xenograft glioblastoma multiform (GBM) braintumors to single fraction radiation therapy. Six metabolites were analyzed with LCModel: alanine (Ala), myo‐inositol (Ins), taurine (Tau), creatine and phosphocreatine (Cr + PCr), glutamine and glutamate (Glu + Gln), and total choline (glycerophosphocholine + phosphocholine) (GPC + PCh). 11 mice received 800 cGy of 200 kVp x‐rays, 5 were untreated controls. PRESS spectra (27 μL volumes) were acquired at multiple time points for treated and control animals. In treated animals, all metabolite : water ratios decreased 3 days post‐treatment, with further decreases at day 7, and then increases at day 14 relative to the 7 day mark. Concentrations on day 7 relative to pre‐treatment were as follows: 0.42 (Ala), 0.43 (Ins), 0.68 (Tau), 0.52 (GPC+PCh), 0.49 (Cr + PCr) and 0.78 (Glu + Gln). Metabolite ratios did not correlate with tumor volume in control animals, suggesting a real therapeutic response was observed. Our 1H MRS data suggests that perturbations in the metabolic signature of GBM cancers occur in response to irradiation. Such changes in the metabolite : water concentration ratios could potentially be exploited for the improvement of radiotherapy.

Glutamine (Gln), glutamate (Glu) and γ-aminobutyric acid (GABA) are relevant brain metabolites that can be measured with magnetic resonance spectroscopy (MRS). This work optimizes the point-resolved spectroscopy (PRESS) sequence echo times, TE1 and TE2 , for improved simultaneous quantification of the three metabolites at 9.4 T. Quantification was based on the proton resonances of Gln, Glu and GABA at ≈2.45, ≈2.35 and ≈2.28 ppm, respectively. Glu exhibits overlap with both Gln and GABA; in addition, the Gln peak is contaminated by signal from the strongly coupled protons of N-acetylaspartate (NAA), which resonate at about 2.49 ppm. J-coupling evolution of the protons was characterized numerically and verified experimentally. A {TE1 , TE2 } combination of {106 ms, 16 ms} minimized the NAA signal in the Gln spectral region, whilst retaining Gln, Glu and GABA peaks. The efficacy of the technique was verified on phantom solutions and on rat brain in vivo. LCModel was employed to analyze the in vivo spectra. The average T2 -corrected Gln, Glu and GABA concentrations were found to be 3.39, 11.43 and 2.20 mM, respectively, assuming a total creatine concentration of 8.5 mM. LCModel Cramer-Rao lower bounds (CRLBs) for Gln, Glu and GABA were in the ranges 14-17%, 4-6% and 16-19%, respectively. The optimal TE resulted in concentrations for Gln and GABA that agreed more closely with literature concentrations compared with concentrations obtained from short-TE spectra acquired with a {TE1 , TE2 } combination of {12 ms, 9 ms}. LCModel estimations were also evaluated with short-TE PRESS and with the optimized long TE of {106 ms, 16 ms}, using phantom solutions of known metabolite concentrations. It was shown that concentrations estimated with LCModel can be inaccurate when combined with short-TE PRESS, where there is peak overlap, even when low (

Proton magnetic resonance spectroscopy (MRS) was used to evaluate the metabolic profile of human glioblastoma multiform brain tumors grown as xenografts in nude mice before, and at multiple time points after single fraction radiation therapy. Tumors were grown over the thigh in 16 mice in this study, of which 5 served as untreated controls and 11 had their tumors treated to 800 cGy with 200 kVp x-rays. Spectra were acquired within 24 h pre-treatment, and then at 3, 7 and 14 d post-treatment using a 9.4 T animal magnetic resonance (MR) system. For the untreated control tumors, spectra (1-2 per mouse) were acquired at different stages of tumor growth. Spectra were obtained with the PRESS pulse sequence using a 3 × 3 × 3 mm(3) voxel. Analysis was performed with the LCModel software platform. Six metabolites were profiled for this analysis: alanine (Ala), myo-inositol (Ins), taurine (Tau), creatine and phosphocreatine (Cr + PCr), glutamine and glutamate (Glu + Gln), and total choline (glycerophosphocholine + phosphocholine) (GPC + PCh). For the treated cohort, most metabolite/water concentration ratios were found to decrease in the short term at 3 and 7 d post-treatment, followed by an increase at 14 d post-treatment toward pre-treatment values. The lowest concentrations were observed at 7 d post-treatment, with magnitudes (relative to pre-treatment concentration ratios) of: 0.42 ± 24.6% (Ala), 0.43 ± 15.3% (Ins), 0.68 ± 27.9% (Tau), 0.52 ± 14.6% (GPC+PCh), 0.49 ± 21.0% (Cr + PCr) and 0.78 ± 24.5% (Glu + Gln). Control animals did not demonstrate any significant correlation between tumor volume and metabolite concentration, indicating that the observed kinetics were the result of the therapeutic intervention. We have demonstrated the feasibility of using MRS to follow multiple metabolic markers over time for the purpose of evaluating therapeutic response of tumors to radiation therapy. This study provides supporting evidence that metabolite/water concentration ratios have the potential to be used as biomarkers for the assessment of the response to therapy.

Purpose 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. Materials and Methods 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. Results 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 (R2 = 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 (R2 = 0.972). Conclusion 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.J. Magn. Reson. Imaging 2013. © 2013 Wiley Periodicals, Inc. J. Magn. Reson. Imaging 2015;41:481–486.© 2013 Wiley Periodicals, Inc.

Proton-decoupled, 13C nuclear MRS experiments require a RF coil that operates at the Larmor frequencies of both 13C and 1H. In this work, we designed, built and tested a single-unit, dual-tuned coil based on a half-birdcage open coil design. It was constructed as a low-pass network with a resonant trap in series with each leg. Traps are tuned in alternate legs such that the two resonant modes arise from currents on alternate legs. The coil performance was compared with that of a dual-tuned coil consisting of two proton surface coils operating in quadrature and a single surface coil for 13C transmission and reception. The half-birdcage coil was shown to produce a more homogeneous RF field at each frequency and was more sensitive to a 13C signal arising from regions further from the coil surface. The applicability of the coil in vivo was demonstrated by acquiring a proton decoupled, natural abundance 13C glycogen signal from the calf of a normal volunteer. Copyright © 2013 John Wiley & Sons, Ltd.

Purpose: To demonstrate, at 9.4 T, that J-coupling interactions exhibited by lipid protons affects lipid composition determination with a point resolved spectroscopy (PRESS) sequence. Materials and Methods: Experiments were conducted on four oils (almond, corn, sesame, and sunflower), on visceral adipose tissue of a euthanized mouse, and on pure linoleic acid at 9.4 T. The 2.1, 2.3, and 2.8 ppm resonances were measured at multiple echo times (TEs) by a standard PRESS sequence and by a PRESS sequence consisting of narrow-bandwidth refocusing pulses designed to rewind the J-coupling evolution of the target peak protons in the voxel of interest. T2 corrections were performed on both groups of data for the three peaks and lipid compositions for the oils and for the mouse tissue were determined. Lipid compositions were also calculated from a short-TE standard PRESS spectrum. Results: A chemical analysis of the samples was not performed; however, the oil compositions calculated from resonance peaks acquired with the PRESS sequence designed to minimize J-coupling effects, following T2 relaxation correction, closely agreed with values in the literature, which was not the case for all of the compositions determined from the regular PRESS spectra. Conclusion: The presented work brings to attention the significance of J-coupling effects when calculating lipid compositions from localized proton spectra. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.

The glycerol methylene proton resonances (4-4.5 parts per million, ppm), which arise from the triglyceride backbone, are relevant to fat composition assessment and can be measured with proton MRS. The purpose of the presented work is to determine long TE (echo time) point resolved spectroscopy (PRESS) and stimulated echo acquisition mode (STEAM) values at 3 T to resolve the glycerol resonances from that of overlapping water. The response of the glycerol methylene protons of nine edible oils as a function of PRESS and STEAM TE (mixing time, TM = 20 ms) was investigated. In addition, high resolution NMR spectra of the oils were acquired at 16.5 T. Long TE values where J-coupling losses were lowest were selected, namely a TE of 180 ms for PRESS (first echo time 17 ms) and a TE of 100 ms for STEAM (mixing time 20 ms). Oil olefinic (≈5.4 ppm) to glycerol ratios were calculated from the long TE spectra and correlated with 16.5 T ratios. The two techniques yielded olefinic/glycerol ratios that correlated with 16.5 T ratios (R2 = 0.79 for PRESS and 0.90 for STEAM). The efficacy of the sequences in resolving the glycerol resonance from that of water was verified in vivo on tibial bone marrow of four healthy volunteers. In addition, the potential for using the glycerol methylene signal normalized to the methyl signal (≈0.9 ppm) to assess changes in free fatty acid content was demonstrated by measuring differences in spectra acquired from a triglyceride peanut oil phantom and from a phantom composed of a mixture of peanut oil and free fatty acid oleic acid.

The purpose of this study is to use magnetic resonance imaging to monitor the response of human glioma tumor xenografts to single fraction radiation therapy. Mice were divided into four treatment groups ( n = 6 per group) that received 50, 200, 400, or 800 cGy of 200 kVp x rays. A fifth group ( n = 6 ) received no radiationdose and served as the control. Quantitative maps of the treatedtumortissue were produced of water apparent diffusion coefficient (ADC) and transverse relaxation time (T2). Mice were imaged before and at multiple time points after treatment. There was a statistically significant difference in tumor growth relative to that of the control for all treatment groups. Only the highest dose group showed T2 values that were significantly different at all measured time points after treatment. In this group, there was an 8.3% increase in T2 relative to controls 2 days after treatment, but when measured 14 days after treatment, mean tumor T2 had dropped to 10.1% below the initial value. ADC showed statistically significant differences from the control at all dose points. A radiationdose dependence was observed. In the highest dose group, the fractional increases in ADC were higher than those observed for T2. ADC was sensitive to radiation-induced changes in lower dose groups that did not have significant T2 change. At all doses, elevation of mean tumor ADC preceded deviations in tumor growth from the control. These observations support the potential application of ADC as a time and dose sensitive marker of tumor response to radiation therapy.

Turbo spectroscopic imaging (TSI) is a spin echo spectroscopic imaging technique in which two or more echoes are acquired per excitation to reduce the acquisition time. The application of TSI has primarily been limited to the detection of uncoupled spins because the signal from coupled spins is modulated as a function of echo time. In this work we demonstrate how the TSI sequence can be modified to observe spins like the C(2) protons of Glx (approximately 3.75 ppm) which are involved solely in weak-coupling interactions. The technique exploits the chemical shift displacement effect by employing TSI refocusing pulses that have bandwidths which are less than the chemical shift difference between the target spins and the spins to which they are weakly coupled. The modified TSI sequence rewinds the J-evolution of the target protons in the slice of interest independently of the echo time or echo spacing, thereby removing any signal variation between successive echoes (apart from T(2) relaxation effects). In this study we tailored the narrow-bandwidth TSI sequence for observation of the C(2) Glx protons. The echo time was experimentally optimized to minimize signal contamination from myo-inositol, and the efficacy of the method was verified on phantom solutions of Glx and on brain in vivo.

Point-resolved spectroscopy (PRESS), characterized by two TEs (TE1 and TE2 ), can be employed to perform animal magnetic resonance spectroscopy (MRS) studies at 9.4 T. Taurine (Tau) and choline (Cho) are relevant metabolites that can be measured by MRS. In this work, the response of the J-coupled protons of Tau as a function of PRESS TE1 and TE2 was characterized at 9.4 T to achieve two objectives. The first was to determine two TE1 and TE2 combinations that could be used to obtain T2 -corrected measures of Tau (3.42 ppm) that were minimally influenced by J coupling. The second was to exploit the Tau J coupling to find a timing combination that minimized the 3.25-ppm Tau signal to enable the Cho (3.22 ppm) resonance to be resolved from the overlapping Tau signal. The response of Tau protons was investigated both numerically and experimentally. It was numerically determined that the timings {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms, 70 ms} yielded similar 3.42-ppm Tau resonance areas (5% difference), rendering them suitable for Tau T2 determination. {TE1 , TE2 } = {25 ms, 50 ms} was found to yield minimal 3.25-ppm Tau signal, reducing its interference with Cho. The efficacy of the timings was demonstrated on phantom solutions and in vivo in four Sprague Dawley rats. LCModel was employed to analyse the in vivo spectra and Tau T2 values were estimated by fitting the Tau peak areas obtained with {TE1 , TE2 } = {17 ms, 10 ms} and {TE1 , TE2 } = {80 ms, 70 ms} to a monoexponentially decaying function. An average Tau T2 of 106 ms (standard deviation, 12 ms) was obtained. LCModel analysis of rat spectra obtained with {TE1 , TE2 } = {25 ms, 50 ms} demonstrated negligible levels of Tau signal, compared with that obtained with short TE.

To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer.Twenty-three patients with low risk disease were enrolled on this active surveillance study, all of which had Gleason score 6 or less disease. All patients had clinical assessments, including digital rectal examination and prostate specific antigen (PSA) testing, every 6 mo with annual 3T mpMRI scans with gadolinium contrast and minimum sextant prostate biopsies. The MRI images were anonymized of patient identifiers and clinical information and each scan underwent radiological review without the other results known. Descriptive statistics for demographics and follow-up as well as the sensitivity and specificity of mpMRI to identify prostate cancer and progressive disease were calculated.During follow-up (median 24.8 mo) 11 of 23 patients with low-risk prostate cancer had disease progression and were taken off study to receive definitive treatment. Disease progression was identified through upstaging of Gleason score on subsequent biopsies for all 11 patients with only 2 patients also having a PSA doubling time of less than 2 years. All 23 patients had biopsy confirmed prostate cancer but only 10 had a positive index of suspicion on mpMRI scans at baseline (43.5% sensitivity). Aggressive disease prediction from baseline mpMRI scans had satisfactory specificity (81.8%) but low sensitivity (58.3%). Twenty-two patients had serial mpMRI scans and evidence of disease progression was seen for 3 patients all of whom had upstaging of Gleason score on biopsy (30% specificity and 100% sensitivity).Addition of mpMRI imaging in active surveillance decision making may help in identifying aggressive disease amongst men with indolent prostate cancer earlier than traditional methods.

A general analytical framework is presented for the design of birdcage radiofrequency resonators on cylindrical formers having arbitrary cross-sectional shape. The primary objective of such shapes would be to improve the sensitivity of the NMR experiment to noncircular regions of the human anatomy while maintaining field homogeneity and quadrature polarization comparable to those of standard circular birdcage coils. The shape of the corresponding radiofrequency screen, which is required to decouple the coil from the rest of the NMR system and which is key to the performance, is also provided by this methodology. The theory was tested by constructing a 3-T, quadrature, proton coil on a shape conforming to the anthropomorphic mean of the human head, namely, the oval of Cassini. Both bench tests (Q) and in vivo spectral and imaging comparisons of the Cassinian coil with an equivalently dimensioned and constructed circular birdcage coil, respectively, predicted and demonstrated in vivo an improvement in SNR of ∼24% over the circular section coil. The experimental RF field homogeneity and quadrature performance were comparable for both coil geometries, with the circular coil being marginally superior. Magn Reson Med 53:201–211, 2005. © 2004 Wiley-Liss, Inc.

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.

Purpose: To investigate the response of taurine (Tau) protons as a function of PRESS echo times, TE1 and TE2, to determine two TE combinations that can be employed to estimate the T2 (transverse relaxation) value of Tau at 9.4 T. The Tau protons are involved in J-coupling interactions; therefore, the two timing combinations should result in similar signal losses due to J-coupling. Methods: Experiments were performed with a 9.4 T animal MRI scanner. Numerical calculations of the response of Tau as a function of PRESS TE1 and TE2 were calculated and two TE combinations that yield a similar area for the 3.42 ppm Tau resonance were selected as optimal. The timings were verified on a 50 mM Tau/10 mM Cr (creatine) phantom. In-vivo experiments were performed on four rats. Spectra were acquired with the timings from a voxel placed in the rat brain and Tau peak areas were fit to monoexponentially decaying functions to obtain T2 values. Results: The PRESS TE combinations selected for Tau T2 determination are {TE1, TE2} = {17 ms, 10 ms} and {80 ms, 70 ms}; the signal yield for the two timings differs by 5 % theoretically. The average Tau T2 for the four rats was found to be 106 ms with a standard deviation of 12 ms. Conclusions: We have demonstrated that acquiring PRESS spectra with {TE1, TE2} = {17 ms, 10 ms} and {TE1, TE2} = {80 ms, 70 ms} enables T2 corrected measures of Tau to be obtained at 9.4 T.

Purpose: To optimize the timings of the magnetic resonance spectroscopy technique, Point RESolved Spectroscopy (PRESS), to resolve glutamine (Gln; ∼2.45ppm) in vivo at 9.4T. The Gln resonance is contaminated by N-acetylaspartate (NAA; ∼2.49ppm) and to a lesser extent by glutathione (GSH; ∼2.51ppm). Methods: Signals of glutamate (Glu; ∼2.35ppm), Gln, and NAA at 9.4T in response to TE (echo time) values of a PRESS sequence were investigated numerically, and the {TE1, TE2} combination that best resolved Gln while retaining Glu was considered optimal. The timings were verified on phantom solutions and in vivo on four Sprague Dawley rat brains. In-vivo spectra were analyzed with LCmodel. Results: An optimal {TE1, TE2} combination was determined to be {106ms, 16ms}, which resulted in simulated peak areas for Glu, Gln, and NAA, of 54%, 42%, and −2%, respectively, of the corresponding shortest {2ms, 2ms} values. Experimentally, the Gln yield with the optimal TE values was found to be ∼54% of that obtained with a short-TE of {TE1, TE2} = {12ms, 9ms}. The yield changed by

The objective of this work is to optimize the Point Resolved Spectroscopy (PRESS) sequence echo times, TE1 and TE2, for glycine (Gly) detection at 9.4 T, a common field strength at which animal magnetic resonance studies are conducted. The two uncoupled protons of Gly resonate at about 3.55 ppm and their peak is largely overwhelmed by signal from the strongly coupled protons of myo-inositol (mI) which resonate in the Gly spectral region (3.52–3.57 ppm). J-coupling evolution of the mI protons was characterized at 9.4 T by numerical calculations and by acquiring PRESS spectra with various {TE1, TE2} combinations from a 50 mM mI phantom. A {TE1, TE2} combination of {60 ms, 100 ms} minimized mI signal in the Gly spectral region and its efficacy was verified on mI and Gly phantom solutions and on rat brain in vivo. LCModel was employed to analyse in vivo spectra. The average Gly concentration from three rat brains was found to be 1.35 mM assuming a creatine (Cr) concentration of 8 mM. LCModel Cramer-Rao Lower Bound values for Gly ranged between 15% and 20%.

Proton-decoupled, (13) C nuclear MRS experiments require a RF coil that operates at the Larmor frequencies of both (13) C and (1) H. In this work, we designed, built and tested a single-unit, dual-tuned coil based on a half-birdcage open coil design. It was constructed as a low-pass network with a resonant trap in series with each leg. Traps are tuned in alternate legs such that the two resonant modes arise from currents on alternate legs. The coil performance was compared with that of a dual-tuned coil consisting of two proton surface coils operating in quadrature and a single surface coil for (13) C transmission and reception. The half-birdcage coil was shown to produce a more homogeneous RF field at each frequency and was more sensitive to a (13) C signal arising from regions further from the coil surface. The applicability of the coil in vivo was demonstrated by acquiring a proton decoupled, natural abundance (13) C glycogen signal from the calf of a normal volunteer.

Purpose: To examine the behavior of lipid olefinic and diallylic resonances as a function of PRESS (point resolved spectroscopy) echo time (TE) to determine an optimal long TE value for their measurement at 3 T. Materials and Methods: Experiments were conducted on nine oils (almond, canola, cod liver, corn, linseed, peanut, sesame, sunflower, and walnut oil) and on vertebral and tibial bone marrow in vivo at 3 T. The methylene (or methyl + methylene), diallylic, and olefinic resonances were measured with PRESS with multiple TEs. Results: J-coupling evolution effects on the olefinic and diallylic peaks appeared to be minimized when TE = 200 msec. The TE = 200 msec olefinic/methylene and diallylic/methylene peak area ratios calculated for each oil correlated well with ratios deduced from oil compositions in the literature (R2 = 0.92 and 0.98 for the olefinic and diallylic protons, respectively). In addition, the relative amounts of bone marrow unsaturation of vertebral and tibial bone marrow inferred from the TE = 200 msec olefinic/(methyl + methylene) peak area ratio agreed with values estimated from the literature. Conclusion: A PRESS sequence with a long TE value of 200 msec is suitable for determining relative amounts of lipid unsaturation at 3 T. J. Magn. Reson. Imaging 2013;37:944–949. © 2012 Wiley Periodicals, Inc.

Purpose: To improve proton magnetic resonance spectroscopy (MRS) transverse relaxation (T2) determination and quantification of lipid methylene chain (1.3 ppm) protons by rewinding their J-coupling evolution. Methods: MRS experiments were performed on four lipid phantoms, namely, almond, corn, sunflower and oleic acid, using a 3 T Philips MRI scanner with a transmit/receive birdcage head coil. Two PRESS (Point RESolved Spectroscopy) pulse sequences were used. The first PRESS sequence employed standard bandwidth (BW) (∼550 Hz) RF (radiofrequency) refocussing pulses, while the second used refocussing pulses of narrow BW (∼50 Hz) designed to rewind J-coupling evolution of the methylene protons in the voxel of interest. Signal was acquired with each sequence from a 5×5×5 mm3 voxel, with a repetition time (TR) of 3000 ms, and with echo times (TE) of 100 to 200 ms in steps of 20 ms. 2048 sample points were measured with a 2000 Hz sampling bandwidth. Additionally, 30 mm outer volume suppression slabs were used to suppress signal outside the voxel of interest. The frequency of the RF pulses was set to that of the methylene resonance. Methylene peak areas were calculated and fitted in MATLAB to a monexponentially decaying function of the form M0exp(-TE/T2), where M0 is the extrapolated area when TE = 0 ms and yields a measure of concentration. Results: The determined values of M0 and T2 increased for all fatty acids when using the PRESS sequence with narrow BW refocussing pulses. M0 and T2 values increased by an average amount (over all the phantoms) of 31% and 14%, respectively. Conclusion: This investigation has demonstrated that J-coupling interactions of lipid methylene protons causes non-negligible signal losses which, if not accounted for, Result in underestimations of their levels and T2 values when performing MRS measurements. Funded by the Natural Sciences and Engineering Research Council of Canada and the Canadian Breast Cancer Foundation - Prairies.NWT

Purpose: To demonstrate how J-coupling modulations of the CH3 lipid resonance can be minimized enabling a representative T2 to be measured. Materials and Methods: Experiments were conducted on canola oil and in vivo on tibial bone marrow of four volunteers at 3 T. The T2 of the CH2 protons was measured with a standard point resolved spectroscopy (PRESS) sequence, whereas the T2 of the CH3 protons was determined with a PRESS sequence composed of narrow bandwidth refocusing pulses designed to exploit the chemical shift displacement effect and rewind the J-coupling evolution of the CH3 protons in the desired voxel. Spectra were acquired at five echo times. Results: The narrow bandwidth PRESS sequence rewound the J-evolution of the CH3 protons resulting in a T2 curve that was well described by a monoexponential function. The mean T2 of the bone marrow CH3 protons was calculated to be 132.6 msec. The mean T2 of the bone marrow CH2 protons was estimated with a regular PRESS sequence to be 88.0 msec. The mean CH2:CH3 tibial bone marrow composition was estimated to be 12.0:1. Conclusion: The presented technique permits the T2 of the methyl protons of lipids to be determined with more accuracy by minimizing contributions from J-coupling. J. Magn. Reson. Imaging 2010;31:1514–1521. © 2010 Wiley-Liss, Inc.

The purpose of this study is to investigate the response of transverse relaxation time (T2) and apparent diffusion coefficient (ADC) in human glioma tumor xenografts during and after fractionated radiotherapy. Tumor-bearing mice were divided into four treatment groups (n=6 per group) that received a total dose of 800 cGy of 200 kVp x-rays, given over two or three fractions, with a fraction spacing of either 24 or 72 h. A fifth treatment group received 800 cGy in a single fraction, and a sixth group of mice served as an untreated control. All mice were scanned pretreatment, before each fraction and at multiple points after treatment using a 9.4 T magnetic resonance imaging (MRI) system. Quantitative T2 and ADC maps were produced. All treated groups showed an increase in mean tumor ADC, though the time for this response to reach a maximum and return toward baseline was delayed in the fractionated groups. The highest ADC was measured 7 days after the final fraction of treatment for all groups. There were no significant differences in the maximum measured change in ADC between any of the treated groups, with the average measured maximum value being 20.5% above baseline. After treatment, all groups showed an increase in mean tumor T2, with the average measured maximum T2 being 4.7% above baseline. This increase was followed by a transition to mean T2 values below baseline values, with the average measured tumor T2 being 92.4% of the pretreatment value. The transition between elevated and depressed T2 values was delayed in the cases of fractionated therapies and occurred between 3.6 and 7.3 days after the last fraction of treatment. These results further the understanding of the temporal evolution of T2 and ADC during fractionated radiotherapy and support their potential use as time-sensitive biomarkers for tumor response.

A PRESS (Point RESolved Spectroscopy) sequence for the improved detection of the C 2 protons of Glx (glutamate and glutamine) at ≈3.75 ppm is presented in this work. It is shown that for spins like the C 2 protons of Glx which are involved solely in weak coupling interactions, the chemical shift displacement effect can be turned to advantage by exploiting PRESS refocusing pulses with bandwidths less than the chemical shift difference between the target spins and the spins to which they are weakly coupled. The narrow-bandwidth PRESS sequence allows refocusing of the J -coupling evolution of the target protons in the voxel of interest independently of echo time yielding signal equivalent to that which can be obtained with a one-pulse acquire sequence (assuming ideal pulses and ignoring T 2 relaxation). The total echo time of PRESS was set long enough for the decay of macromolecule signal and the two echo times were empirically optimized so that the Glx signal at 3.75 ppm suffered minimal contamination from myo-inositol. The efficacy of the method was verified on phantom solutions of Glx and on brain in vivo .

The effect of strong homonuclear proton coupling on 1 3 C incorporation measurements by either indirect or direct means was investigated (and illustrated with glutamate) both numerically and experimentally at 3.0 T. In particular, two sequences were considered, each using a proton PRESS sequence for localization. The indirect 1 3 C detection method incorporated the POCE (proton observe carbon edited) technique onto PRESS, and for direct 1 3 C detection a DEPT (distortionless enhancement by polarization transfer) sequence was appended to the PRESS localization. Both analysis and experiment demonstrate that when strong homonuclear coupling of protons is additional to heteronuclear coupling with 1 3 C spins, the 1 3 C measures derived from either the indirect PRESS-POCE sequence or the direct-but-enhanced PRESS-DEPT sequence are significantly modified. Specifically, the MR lineshapes of both 1 3 C-bonded and nonbonded protons are changed during 1 3 C incorporation, giving rise, for example, to a potential cross-contamination of

Proton magnetic resonance spectroscopy (MRS) of vertebral lipids has been shown to be relevant in the study of cancer. The olefinic resonance (≈ 5.4 ppm) yields a measure of lipid unsaturation. However, its measurement with standard short echo time (TE) MRS sequences is difficult due to the large overlapping water signal. The purpose of this work is to optimize the TE of a PRESS (Point RESolved Spectroscopy) sequence to measure the olefinic resonance from spinal bone marrow with minimal losses due to J-coupling and minimal contamination from water at 3 T, a field strength becoming more common in the clinic. Experiments were conducted on nine oils and on L4 vertebral bone marrow in vivo at 3 T. The methylene (or methyl + methylene), and olefinic resonances were measured with PRESS using multiple TEs. The effects of J-coupling evolution of the olefinic protons appeared to be minimal when TE = 200 ms. The TE = 200 ms olefinic/methylene peak area ratios calculated for each oil correlated well with ratios deduced from oil compositions in the literature (R2 = 0.92). The TE = 200 ms PRESS spectra obtained from vertebra of four volunteers showed negligible contribution from water to the olefinic resonance, thereby enabling the olefinic peak area to be quantified more accurately. The results of this work demonstrate that a PRESS sequence with TE = 200 ms is suitable for measuring relative levels of lipid unsaturation and for resolving the olefinic resonance from contaminating water signal in spinal bone marrow.

Purpose: To improve lipid composition determination by localized protonmagnetic resonancespectroscopy (MRS) at 9.4 T by minimizing J‐coupling modulations of the 2.1 ppm, 2.3 ppm, and 2.8 ppm lipid peaks. Methods: Experiments were conducted on corn oil and sesame oil phantoms at 9.4 T. A regular PRESS (Point RESolved Spectroscopy)sequence was used to obtain spectra from the oils with echo times (TEs) of 20, 30, 40, 50, 80, 120, 180, and 240 ms. A modified PRESS sequence designed to minimize signal losses due to J‐coupling was also utilized to acquire spectra of the 2.1 ppm, 2.3 ppm, and 2.8 ppm resonances of the oils with TEs of 40, 50, 80, 120, 180 and 240 ms. The areas of the three lipid resonances obtained by both sequences were plotted as a function of echo time and the resulting curves were fitted to the function Moexp(−TE/T2), where Mo is proportional to the proton concentration of the target resonance. Oil compositions (% linoleic acid, % oleic acid, and % saturated fatty acids) were determined from extrapolated Mo values for the three resonances and from equations established in the literature. Results: The responses of the three proton groups to a regular PRESS sequence were modulated due to J‐coupling interactions. However, the responses to the modified PRESS sequence fit well to monoexponentially decaying functions. Oil compositions determined with the PRESS sequence designed to minimize J‐coupling effects agreed with results reported in the literature unlike those calculated from spectra acquired with the regular PRESS sequence. Conclusions: Lipid compositions determined by localized proton MRS can contain significant errors (as high as 49 %), even if they are determined from short‐ TE PRESS spectra corrected for T2 relaxation, if the influence of J‐coupling is not considered.

Purpose: To improve the accuracy of lipid CH2/CH3 ratios determined by protonmagnetic resonancespectroscopy (MRS) by minimizing J‐coupling modulations of the CH3lipid peak. Method and Materials: Experiments were conducted in vivo on the tibial bone marrow lipids of four volunteers at 3 T. A regular PRESS (Point RESolved Spectroscopy)sequence was used to estimate the T2 (transverse relaxation) of the CH2protons by acquiring spectra at five echo times (TEs) and plotting the areas as a function of TE. The curve was fitted to the function Moexp(−TE/T2) where M0 is proportional to the CH2proton concentration. The CH3 response to a regular PRESS sequence is modulated due to J‐coupling interactions and does not decay monotonically. To determine Mo of the CH3protons a narrow‐bandwidth PRESS sequence was designed that rewinds the J‐coupling evolution of the CH3protons in the voxel of interest and spectra were acquired with the same five TEs. The CH2/CH3 ratio was calculated by dividing the CH2 Mo by that determined for CH3 and the result was multiplied by 1.5 to compensate for the different proton multiplicities. Results: The mean T2 of the CH2protons was estimated to be ≈ 88 ms. Applying the narrow‐bandwidth PRESS sequence minimized CH3 signal variations due to J‐coupling and resulted in a decay curve that could be described by a monoexponential T2 decay function. The mean T2 for the CH3protons was ≈ 133 ms. A mean ratio of 12:1 was calculated for the CH2:CH3 ratio of the tibial bone marrow lipids of all volunteers. Conclusion: The presented PRESS sequence enables the T2 of the CH3lipidprotons to be measured with more accuracy than would be determined by using short‐TEs thereby allowing a more accurate measure of the CH2/CH3lipid composition ratio to be determined.

A 9.4T MRI system was used to serially monitor the apparent diffusion coefficient (ADC) and transverse relaxation time (T2) of human glioblastoma multiforme (GBM) tumours grown in mice. The temporal and dose dependence of these parameters was studied in groups of mice ( n =6 per group) that were treated with a single fraction of 200 kVp x‐rays of varying dose (50, 200, 400, or 800 cGy). An untreated control group was also observed using the same MRI scheme. To further examine the sensitivity of these parameters, an additional group of six mice were treated with two fractions of 400 cGy separated by 72 hours and monitored by MRI before, between, and after the two fractions. A relative increase in ADC was observed in all treated groups after irradiation. The relative increase in ADC was positively correlated with treatment dose. At two weeks post‐treatment, the ADC did not return to baseline, but showed further increase. Relative T2 change was less than the relative ADC change for all treatment groups, and a significant response was not observed at all doses. T2 increased in the 800 cGy group two days after treatment, but had fallen below the pretreatment value two weeks after treatment. The response of the 2×400 cGy group agrees with the ADC and T2 response of the 1×400 cGy group during the interfraction period, and is consistent with the 1×800 cGy response after the second fraction, though lagging temporally by approximately the time between fractions.