Estimating relative diglyceride to triglyceride content with localized MRS at 3 T.

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 (R2 > 0.99).

Resolving the omega-3 methyl resonance with long echo time magnetic resonance spectroscopy in mouse adipose tissue at 9.4 T.

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.

Long TE PRESS and STEAM for measuring the triglyceride glycerol CH2 protons at 3 T.

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.

PRESS timings for resolving 13 C4 -glutamate 1 H signal at 9.4 T: Demonstration in rat with uniformly labelled 13 C-glucose.

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. Cramér-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.

Improved resolution of glutamate, glutamine and γ-aminobutyric acid with optimized point-resolved spectroscopy sequence timings for their simultaneous quantification at 9.4 T.

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 Cramér-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 (<20%) CRLBs are reported.

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

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.

Characterization of the response of taurine protons to PRESS at 9.4 T for Resolving choline and Determining taurine T2.

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.

Effect of J coupling on 1.3-ppm lipid methylene signal acquired with localised proton MRS at 3 T.

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.

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

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 (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). 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.

A dual-tuned transceive resonator for (13) C{(1) H} MRS: two open coils in one.

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.

Long echo time proton magnetic resonance spectroscopy for estimating relative measures of lipid unsaturation at 3 T.

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 (R(2) = 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.

Early Metabolic Changes in 1H-MRSI Predictive for Survival in Patients With Newly Diagnosed High-grade Glioma.

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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Effect of J-coupling on lipid composition determination with localized proton magnetic resonance spectroscopy at 9.4 T.

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. T(2) 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 T(2) 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.

T(2) determination of the J-coupled methyl protons of lipids: In vivo ilustration with tibial bone marrow at 3 T.

PURPOSE: To demonstrate how J-coupling modulations of the CH(3) lipid resonance can be minimized enabling a representative T(2) 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 T(2) of the CH(2) protons was measured with a standard point resolved spectroscopy (PRESS) sequence, whereas the T(2) of the CH(3) 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 CH(3) protons in the desired voxel. Spectra were acquired at five echo times. RESULTS: The narrow bandwidth PRESS sequence rewound the J-evolution of the CH(3) protons resulting in a T(2) curve that was well described by a monoexponential function. The mean T(2) of the bone marrow CH(3) protons was calculated to be 132.6 msec. The mean T(2) of the bone marrow CH(2) protons was estimated with a regular PRESS sequence to be 88.0 msec. The mean CH(2):CH(3) tibial bone marrow composition was estimated to be 12.0:1. CONCLUSION: The presented technique permits the T(2) of the methyl protons of lipids to be determined with more accuracy by minimizing contributions from J-coupling.

Temporal and dose dependence of T2 and ADC at 9.4 T in a mouse model following single fraction radiation therapy.

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 radiation dose and served as the control. Quantitative maps of the treated tumor tissue 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 radiation dose 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.

Exploiting the chemical shift displacement effect in the detection of glutamate and glutamine (Glx) with PRESS.

A PRESS (Point RESolved Spectroscopy) sequence for the improved detection of the C2 protons of Glx (glutamate and glutamine) at approximately 3.75ppm is presented in this work. It is shown that for spins like the C2 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 T2 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 3.75ppm suffered minimal contamination from myo-inositol. The efficacy of the method was verified on phantom solutions of Glx and on brain in vivo.

Incorporating homonuclear polarization transfer into PRESS for proton spectral editing: illustration with lactate and glutathione.

A proton spectral editing pulse sequence for the detection of metabolites with spin systems that involve weak coupling is presented. The sequence is based on homonuclear polarization transfer incorporated into the standard PRESS (Point RESolved Spectroscopy) sequence, which is a volume-selective double spin echo method, to enable spatial localization. All peaks in the region of interest are initially suppressed whether they are peaks from the target metabolite or from contaminating background. The target signal is then restored by polarization transfer from a proton that has a resonance outside the suppressed region and to which the target spins are weakly coupled. This is achieved by the application of a 90 degrees hard pulse with phase orthogonal to that of the PRESS excitation pulse at the location of the first echo in PRESS and by optimizing the two PRESS timings, TE(1) and TE(2), for most efficient yield. Background signal not coupled to any protons outside the initially saturated region remains suppressed. The advantage of this sequence compared to multiple quantum filters is that signal from singlet peaks outside the suppressed area are preserved and can thus be used as a reference. The efficacy of the sequence was verified experimentally on phantom solutions of lactate and glutathione at 3.0 T. For the AX(3) spin system of lactate, the sequence timings were optimized by product operator calculations whereas for the ABX spin system of the cysteinyl group of glutathione numerical calculations were performed for sequence timing optimization.

Role of serial multiparametric magnetic resonance imaging in prostate cancer active surveillance.

AIM: To examine whether addition of 3T multiparametric magnetic resonance imaging (mpMRI) to an active surveillance protocol could detect aggressive or progressive prostate cancer. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Monitoring T2 and ADC at 9.4 T following fractionated external beam radiation therapy in a mouse model.

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.