Fast bias-corrected conductivity mapping using stimulated echoes.

OBJECTIVE: To demonstrate the potential of a double angle stimulated echo (DA-STE) method for fast and accurate "full" homogeneous Helmholtz-based electrical properties tomography using a simultaneous B 1 + magnitude and transceive phase measurement. METHODS: The combination of a spin and stimulated echo can be used to yield an estimate of both B 1 + magnitude and transceive phase and thus provides the means for "full" EPT reconstruction. An interleaved 2D acquisition scheme is used for rapid acquisition. The method was validated in a saline phantom and compared to a double angle method based on two single gradient echo acquisitions (GRE-DAM). The method was evaluated in the brain of a healthy volunteer. RESULTS: The B 1 + magnitude obtained with DA-STE showed excellent agreement with the GRE-DAM method. Conductivity values based on the "full" EPT reconstruction also agreed well with the expectations in the saline phantom. In the brain, the method delivered conductivity values close to literature values. DISCUSSION: The method allows the use of the "full" Helmholtz-based EPT reconstruction without the need for additional measurements. As a result, quantitative conductivity values are improved compared to phase-based EPT reconstructions. DA-STE is a fast complex- B 1 + mapping technique that could render EPT clinically relevant at 3 T.

The effects of field strength on stimulated echo and motion-compensated spin-echo diffusion tensor cardiovascular magnetic resonance sequences.

BACKGROUND: In-vivo diffusion tensor cardiovascular magnetic resonance (DT-CMR) is an emerging technique for microstructural tissue characterization in the myocardium. Most studies are performed at 3T, where higher signal-to-noise ratio (SNR) should benefit this signal-starved method. However, a few studies have suggested that DT-CMR is possible at 1.5T, where echo planar imaging artifacts may be less severe and 1.5T hardware is more widely available. METHODS: We recruited 20 healthy volunteers and performed mid-ventricular short-axis DT-CMR at 1.5T and 3T. Acquisitions were performed at peak systole and end-diastole using both stimulated echo acquisition mode (STEAM) and motion-compensated spin-echo (MCSE) sequences at matched spatial resolutions. DT-CMR parameters were averaged over the left ventricle and compared between 1.5T and 3T sequences using both datasets with and without the blow reference data included. RESULTS: Eleven (1.5T) and 12 (3T) diastolic MCSE acquisitions were rejected as the helix angle (HA) demonstrated <50% normal appearance circumferentially or the acquisition was abandoned due to poor image quality; a maximum of one acquisition was rejected for other datasets. Subjective HA map quality was significantly better at 3T than 1.5T for STEAM (p < 0.05), but not for MCSE and other DT-CMR quality measures were consistent with improvements in STEAM at 3T over 1.5T. When blow data were excluded, no significant differences in mean diffusivity were observed between field strengths, but fractional anisotropy was significantly higher at 1.5T than 3T for STEAM systole (p < 0.05). Absolute second eigenvector orientation (E2A, sheetlet angle) was significantly higher at 1.5T than 3T for MCSE systole and STEAM diastole, but significantly lower for STEAM systole (all p < 0.05). Transmural HA distribution was less steep at 1.5T than 3T for STEAM diastole data (p < 0.05). SNR was higher at 3T than 1.5T for all acquisitions (p < 0.05). CONCLUSION: While 3T provides benefits in terms of SNR, both STEAM and MCSE can be performed at 1.5T. However, MCSE is unreliable in diastole at both field strengths and STEAM benefits from the improved SNR at 3T over 1.5T. Future clinical research studies may be able to leverage the wider availability of 1.5T CMR hardware where MCSE acquisitions are desirable.

MISSTEC-S: A fast 1H pulse calibration from spectra simultaneously produced by a spin echo and a stimulated echo.

Radio-Frequency (RF) pulse calibration is an essential step in guaranteeing both optimum acquisition quality in multi-pulse NMR and accurate results in quantitative experiments. Most existing methods are based on a series of spectra for which the flip angle of one or more pulses is progressively incremented, implying a significant experiment time. In order to circumvent this drawback, we have previously proposed an approach based on the acquisition of a spin echo and a stimulated echo - the MISSTEC sequence - which requires only 8 s to determine the PW90-1H, while it is several minutes in the case of the use of a nutation curve. In this work, a new sequence for RF calibration is presented: MISSTEC-S. It is derived from the previously proposed MISSTEC sequence, but the observation of echoes in presence of magnetic field gradient is replaced by the observation of FIDs. This modification allows both spectra to be phased, while imposing a strong constraint on the Mixing Time (TM). However, the relationship used to calculate the flip angle is only correct when TM is small enough to neglect longitudinal relaxation during this delay. In order to reduce TM, the first FID is truncated during acquisition and subsequently lengthened using points from the second FID. Results obtained with MISSTEC-S were compared to those obtained from a complete nutation curve and an excellent correlation was observed, although the experimental time to obtain the PW90 is dramatically reduced.

Improvements in Between-Vendor MRI Harmonization of Renal T2 Mapping using Stimulated Echo Compensation.

BACKGROUND: T2 mapping is valuable to evaluate pathophysiology in kidney disease. However, variations in T2 relaxation time measurements across MR scanners and vendors may occur requiring additional correction. PURPOSE: To harmonize renal T2 measurements between MR vendor platforms, and use an extended-phase-graph-based fitting method ("StimFit") to correct stimulated echoes and reduce between-vendor variations. STUDY TYPE: Prospective. SUBJECTS: 8 healthy "travelling" volunteers (37.5% female, 32 ± 6 years) imaged on four MRI systems across three vendors at four sites, 10 healthy volunteers (50% female, 32 ± 8 years) scanned multiple times on a given MR scanner for repeatability evaluation. ISMRM/NIST system phantom scanned for evaluation of T2 accuracy. FIELD STRENGTH/SEQUENCE: 3T, multiecho spin-echo sequence. ASSESSMENT: T2 images fit using conventional monoexponential fitting and "StimFit." Mean absolute percentage error (MAPE) of phantom measurements with reference T2 values. Average cortex and medulla T2 values compared between MR vendors, with masks obtained from T2 -weighted images and T1 maps. Full-width-at-half-maximum (FWHM) T2 distributions to evaluate local homogeneity of measurements. STATISTICAL TESTS: Coefficient of variation (CV), linear mixed-effects model, analysis of variance, student's t-tests, Bland-Altman plots, P-value <0.05 considered statistically significant. RESULTS: In the ISMRM/NIST phantom, "StimFit" reduced the MAPE from 4.9%, 9.1%, 24.4%, and 18.1% for the four sites (three vendors) to 3.3%, 3.0%, 6.6%, and 4.1%, respectively. In vivo, there was a significant difference in kidney T2 measurements between vendors using a monoexponential fit, but not with "StimFit" (P = 0.86 and 0.92, cortex and medulla, respectively). The intervendor CVs of T2 measures were reduced from 8.0% to 2.6% (cortex) and 7.1% to 2.8% (medulla) with StimFit, resulting in no significant differences for the CVs of intravendor repeat acquisitions (P = 0.13 and 0.05). "StimFit" significantly reduced the FWHM of T2 distributions in the cortex and whole kidney. DATA CONCLUSION: Stimulated-echo correction reduces renal T2 variation across MR vendor platforms. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 1.

GABA, glutamate and excitatory-inhibitory ratios measured using short-TE STEAM MRS at 7-Tesla: Effects of macromolecule basis sets and baseline parameters.

Rationale and objectives: Macromolecules (MMs) affect the precision and accuracy of neurochemical quantification in magnetic resonance spectroscopy. A measured MM basis is increasingly used in LCModel analysis combined with a spline baseline, whose stiffness is controlled by a parameter named DKNTMN. The effects of measured MM basis and DKNTMN were investigated. Materials and methods: Twenty-six healthy subjects were prospectively enrolled and scanned twice using a short echo-time Stimulated Echo Acquisition Mode (STEAM) at 7-T. Using LCModel, analyses were conducted using the simulated MM basis (MMsim) with DKNTMN 0.15 and an MM basis measured inhouse (MMmeas) with DKNTMN of 0.15, 0.30, 0.60 and 1.00. Cramér-Rao lower bound (CRLB) and the concentrations of gamma-aminobutyric acid (GABA), glutamate and excitatory-inhibitory ratio (EIR), in addition to MMs were statistically analyzed. Measurement stability was evaluated using coefficient of variation (CV). Results: CRLBs of GABA were significantly lower when using MMsim than MMmeas; those of glutamate were 2-3. GABA concentrations were significantly higher in the analysis using MMsim than MMmeas where concentrations were significantly higher with DKNTMN of 0.15 or 0.30 than 0.60 or 1.00. Difference in glutamate concentration was not significant. EIRs showed the same difference as in GABA depending on the DKNTMN values. CVs between test-retest scans were relatively stable for glutamate but became larger as DKNTMN increased for GABA and EIR. Conclusion: Neurochemical quantification depends on the parameters of the basis sets used for fitting. Analysis using MMmeas with DKNTMN of 0.30 conformed best to previous studies and is recommended.

Time-dependent diffusion MRI using multiple stimulated echoes.

PURPOSE: To develop a time-efficient pulse sequence that acquires multiple diffusion-weighted images with distinct diffusion times in a single shot by using multiple stimulated echoes (mSTE) with variable flip angles (VFA). METHODS: The proposed diffusion-weighted mSTE with VFA (DW-mSTE-VFA) sequence begins with two 90° RF pulses that straddle a diffusion gradient lobe (GD ) to excite and restore one half of the magnetization into the longitudinal axis. The restored longitudinal magnetization was successively re-excited by a series of RF pulses with VFA, each followed by another GD , to generate a set of stimulated echoes. Each of the multiple stimulated echoes was acquired with an EPI echo train. As such, the train of multiple stimulated echoes produced a set of diffusion-weighted images with varying diffusion times in a single shot. This technique was experimentally demonstrated on a diffusion phantom, a fruit, and healthy human brain and prostate at 3 T. RESULTS: In the phantom experiment, the mean ADC measured at different diffusion times using DW-mSTE-VFA were highly consistent (r = 0.999) with those from a commercial spin-echo diffusion-weighted EPI sequence. In the fruit and brain experiments, DW-mSTE-VFA exhibited similar diffusion-time dependence to a standard diffusion-weighted stimulated echo sequence. The ADC showed significant time dependence in the human brain (p = 0.003 in both white matter and gray matter) and prostate tissues (p = 0.003 in both peripheral zone and central gland). CONCLUSION: DW-mSTE-VFA offers a time-efficient tool for investigating the diffusion-time dependency in diffusion MRI studies.

Radio-frequency pulse calibration using the MISSTEC sequence.

NMR sequences are composed of multiple radio-frequency pulses. Probe adjustment, sample concentration and solvent influence the loading factor, therefore these parameters also impact the validity of flip angles. The commonly used method to calibrate RF pulses is to measure a nutation curve by varying the pulse duration. However, this method is impacted by off-resonance effects, radiation damping and B1 and B0 inhomogeneities. Furthermore, it is important to avoid partial saturation. In this work, the MISSTEC sequence is proposed for pulse calibration. This sequence takes only 8 s or 2 min for 1H or 13C calibration, respectively. High accuracy (with an error below 1%) was obtained for both nuclei. Therefore, the calibrations can be done rapidly and accurately. Furthermore, the MISSTEC measurement could be performed on each sample - in an automated way- before acquisitions, after which the calibration found could be automatically used.

Mapping pH using stimulated echoes formed via chemical exchange.

PURPOSE: RACETE (refocused acquisition of chemical exchange transferred excitations) is a recently developed approach to imaging solute exchange with water. However, it lacks biophysical specificity, as it is sensitive to exchange rates, relaxation rates, solute concentration, and macromolecular content. We modified this sequence and developed a protocol and corresponding metric with specific sensitivity to the solute exchange rate and hence a means for mapping pH. THEORY AND METHODS: RACETE splits the two gradients traditionally used in a stimulated-echo sequence into one applied after exciting solutes and one applied after exciting water, hence requiring exchange for echo formation. In this work, we leverage the dependence of the stimulated-echo signal on the exchange process. By preserving the total irradiation power and using a ratio metric, the other signal dependencies cancel, leaving a specific measure of exchange rate. Additionally, artifacts due to off-resonance excitation of water are addressed using a phase cancelling approach; and a gradient-echo imaging sequence with a variable flip angle excitation is tailored for a fast read-out of RECETE prepared signals. This method is validated using numerical simulations and salicylic acid phantom experiments at 9.4 T. RESULTS: Numerical simulations and phantom experiments demonstrate that the ratio-metric is a single-variable function of exchange rate with extremely low dependence on confounding factors. Additionally, artifacts due to direct water excitation are removed and robustness to B0 and B1 inhomogeneities is demonstrated. CONCLUSION: The proposed method can be used for fast pH mapping with robustness against the confounding effects that widely exist in other methods.

Clinical usefulness of 2-hydroxyglutarate as a biomarker in IDH-mutant chondrosarcoma.

Background: Chondrosarcoma is a common form of malignant bone tumor with limited treatment options. Approximately half of chondrosarcomas harbor gain-of-function mutations in isocitrate dehydrogenase (IDH), and mutant IDH produces 2-hydroxyglutarate (2-HG), which is an oncometabolite that contributes to malignant transformation. Therefore, inhibiting 2-HG production is a novel and promising treatment for advanced chondrosarcoma. 2-HG is also expected to be a useful biomarker for the diagnosis and treatment of IDH-mutant tumors. However, few studies have confirmed this using chondrosarcoma clinical specimens. Non-invasive monitoring of 2-HG levels is useful to infer that mutant IDH inhibitors reach therapeutic targets and to confirm their therapeutic efficacy in clinical practice. Methods: To evaluate the clinical utility of 2-HG as a surrogate biomarker for diagnosis and therapeutic efficacy, we measured intra-tumor and serum levels of 2-HG using frozen tissues and peripheral blood from patients with chondrosarcoma. We also developed a non-invasive method to detect intra-tumor 2-HG signals in vivo using magnetic resonance spectroscopy (MRS). Results: Both intratumoral and serum 2-HG levels were significantly elevated in IDH-mutant tumors, and these levels correlated with decreased survival. Furthermore, we detected intratumoral 2-HG peaks using MR spectroscopy in a xenograft model of IDH-mutant chondrosarcoma, and observed that 2-HG peak signals disappeared after administering an inhibitor of mutant IDH1. Conclusions: Our findings suggest that both intratumoral and serum 2-HG levels represent potentially useful biomarkers for IDH-mutant tumors and that the 2-HG signal in MR spectra has potential value as a non-invasive biomarker. Taken together, these findings may positively impact the clinical development of mutant IDH inhibitors for the treatment of advanced chondrosarcoma.

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).

BUDA-MESMERISE: Rapid acquisition and unsupervised parameter estimation for T1 , T2 , M0 , B0 , and B1 maps.

PURPOSE: Rapid acquisition scheme and parameter estimation method are proposed to acquire distortion-free spin- and stimulated-echo signals and combine the signals with a physics-driven unsupervised network to estimate T1 , T2 , and proton density (M0 ) parameter maps, along with B0 and B1 information from the acquired signals. THEORY AND METHODS: An imaging sequence with three 90° RF pulses is utilized to acquire spin- and stimulated-echo signals. We utilize blip-up/-down acquisition to eliminate geometric distortion incurred by the effects of B0 inhomogeneity on rapid EPI acquisitions. For multislice imaging, echo-shifting is applied to utilize dead time between the second and third RF pulses to encode information from additional slice positions. To estimate parameter maps from the spin- and stimulated-echo signals with high fidelity, 2 estimation methods, analytic fitting and a novel unsupervised deep neural network method, are developed. RESULTS: The proposed acquisition provided distortion-free T1 , T2 , relative proton density (M0), B0 , and B1 maps with high fidelity both in phantom and in vivo brain experiments. From the rapidly acquired spin- and stimulated-echo signals, analytic fitting and the network-based method were able to estimate T1 , T2 , M0 , B0 , and B1 maps with high accuracy. Network estimates demonstrated noise robustness owing to the fact that the convolutional layers take information into account from spatially adjacent voxels. CONCLUSION: The proposed acquisition/reconstruction technique enabled whole-brain acquisition of coregistered, distortion-free, T1 , T2 , M0 , B0 , and B1 maps at 1 × 1 × 5 mm3 resolution in 50 s. The proposed unsupervised neural network provided noise-robust parameter estimates from this rapid acquisition.

Saltiness perception enhancement of fish meat treated by microwave: The significance of conformational characteristics, water and sodium mobility.

A saltiness perception enhancement method of grass carp meat conducted by microwave heating was investigated. Ion chromatographic results demonstrated that all samples had the same sodium level retained in matrices after being treated by water bath (WBV) and microwave with different power of 2.5, 7.5, 10, and 12.5 W/g (MWV). However, the meat treated by microwave exhibited a higher salty intensity than that of WBV, particularly MWV-10 W/g and MWV-12.5 W/g. The enhanced saltiness perception of meat treated by microwave was attributed to the facilitated water and sodium mobility demonstrated by low field-NMR and pulse-field-gradient stimulated echo (PFG-STE) 23Na NMR experiments. Furthermore, the enhancement was also related to the formation of microstructure favorable for sodium diffusion, originating from the insufficient denaturation and less exposure of hydrophobic groups of proteins induced by microwave heating. Therefore, microwave heating has the potential to enhance the saltiness perception of meat in the food industry.

Repeatability of proton magnetic resonance spectroscopy of the brain at 7 T: effect of scan time on semi-localized by adiabatic selective refocusing and short-echo time stimulated echo acquisition mode scans and their comparison.

BACKGROUND: Proton magnetic resonance spectroscopy (MRS) provides a unique opportunity for in vivo measurements of the brain's metabolic profile. Two methods of mainstream data acquisition are compared at 7 T, which provides certain advantages as well as challenges. The two representative methods have seldom been compared in terms of measured metabolite concentrations and different scan times. The current study investigated proton MRS of the posterior cingulate cortex using a semi-localized by adiabatic selective refocusing (sLASER) sequence and a short echo time (TE) stimulated echo acquisition mode (sSTEAM) sequence, and it compared their reliability and repeatability at 7 T using a 32-channel head coil. METHODS: Sixteen healthy subjects were prospectively enrolled and scanned twice with an off-bed interval between scans. The scan parameters for sLASER were a TR/TE of 6.5 s/32 ms and 32 and 48 averages (sLASER×32 and sLASER×48, respectively). The scan parameters for sSTEAM were a TR/TE of 4 s/5 ms and 32, 48, and 64 averages (sSTEAM4×32, sSTEAM4×48, and sSTEAM4×64, respectively) in addition to that with a TR/TE of 8 s/5 ms and 32 averages (sSTEAM8×32). Data were analyzed using LCModel. Metabolites quantified with Cramér-Rao lower bounds (CRLBs) >50% were classified as not detected, and metabolites quantified with mean or median CRLBs ≤20% were included for further analysis. The SNR, CRLBs, coefficient of variation (CV), and metabolite concentrations were statistically compared using the Shapiro-Wilk test, one-way ANOVA, or the Friedman test. RESULTS: The sLASER spectra for N-acetylaspartate + N-acetylaspartylglutamate (tNAA) and glutamate (Glu) had a comparable or higher SNR than sSTEAM spectra. Ten metabolites had lower CRLBs than prefixed thresholds: aspartate (Asp), γ-aminobutyric acid (GABA), glutamine (Gln), Glu, glutathione (GSH), myo-inositol (Ins), taurine (Tau), the total amount of phosphocholine + glycerophosphocholine (tCho), creatine + phosphocreatine (tCr), and tNAA. Performance of the two sequences was satisfactory except for GABA, for which sLASER yielded higher CRLBs (≥18%) than sSTEAM. Some significant differences in CRLBs were noted, but they were ≤2% except for GABA and Gln. Signal averaging significantly lowered CRLBs for some metabolites but only by a small amount. Measurement repeatability as indicated by median CVs was ≤10% for Gln, Glu, Ins, tCho, tCr, and tNAA in all scans, and that for Asp, GABA, GSH, and Tau was ≥10% under some scanning conditions. The CV for GABA according to sLASER was significantly higher than that according to sSTEAM, whereas the CV for Ins was higher according to sSTEAM. An increase in signal averaging contribute little to lower CVs except for Ins. CONCLUSIONS: Both sequences quantified brain metabolites with a high degree of precision and repeatability. They are comparable except for GABA, for which sSTEAM would be a better choice.

Varying diffusion time to discriminate between simulated skeletal muscle injury models using stimulated echo diffusion tensor imaging.

PURPOSE: Evaluate the relationship between muscle microstructure, diffusion time (Δ), and the diffusion tensor (DT) to identify the optimal Δ where changes in muscle fiber size may be detected. METHODS: The DT was simulated in models with histology informed geometry over a range of Δ with a stimulated echo DT imaging (DTI) sequence using the numerical simulation application DifSim. The difference in the DT at each Δ between healthy and injured skeletal muscle models was calculated, to identify the optimal Δ at which changes in muscle fiber size may be detected. The random permeable barrier model (RPBM) was used to estimate muscle microstructure from the simulated DT measurements, which were compared to the ground truth. RESULTS: Across all models, fractional anisotropy provided greater contrast between injured and control models than diffusivity measurements. Compared to control models, in atrophic injury models, the greatest difference in the DT was found between 90 ms and 250 ms. In models with acute edema, the contrast between injured and control muscle increased with increasing diffusion time, although these models had smaller mean fiber areas. RPBM systematically underestimated fiber size but accurately estimated surface area-to-volume ratio of simulated models. CONCLUSION: These findings may better inform pulse sequence parameter selection when performing DTI experiments in vivo. If only a single diffusion experiment can be performed, the selected Δ should be ~170 ms to maximize the ability to discriminate between different injury models. Ideally several diffusion times between 90 ms and 500 ms should be sampled in order to maximize diffusion contrast, particularly when the disease process is unknown.

Detecting Mild Lower-limb Skeletal Muscle Fatigue with Stimulated-echo q-space Imaging.

The feasibility of detecting mild exercise-related muscle fatigue via stimulated echo (STE) and q-space imaging (qsi) was evaluated. The right calves of seven healthy volunteers were subjected to mild exercise loading, and qsi was generated using spin echo (Δ: 45.6 ms) and three different STE (Δ: 114, 214, and 414 ms) acquisitions. We concluded that qsi with an increased STE diffusion time can detect mild fatigue in the gastrocnemius muscle.

Background suppressed magnetization transfer MRI.

PURPOSE: Up to 30% of the hydrogen atoms in brain tissue are part of molecules ("semisolids") other than water. In MRI, their magnetization is typically not observed directly, but can influence the water magnetization through magnetization transfer (MT). Comparison of MRI scans differentially sensitized to MT allows estimation of the semisolid fraction and potential changes with disease. Here, we present an approach designed to improve this estimate by measuring the size of the MT effect in a single scan. METHODS: A stimulated echo sequence was used to generate a spatial pattern in the longitudinal water magnetization, which was then given time to exchange with semisolids. After saturating the remaining water magnetization, reverse exchange was allowed to partly re-establish the original water magnetization pattern. The third excitation pulse then formed a stimulated echo out of this pattern. RESULTS: MT data were obtained on 10 human subjects at 7 T with varying exchange times. The images showed the expected time dependence of signal associated with the forward and reverse exchange processes. Excellent suppression of non-exchanging background signal was achieved. As expected, this suppression came at the price of a substantial reduction in exchange-related signal (by ~75% compared to the signal in saturation recovery MT), in part because of the reliance on a 2-step exchange process. CONCLUSION: The results demonstrate an MT signal can be observed in a single acquisition without subtraction. This may be advantageous for MT measurements when signal instabilities related to motion and physiological variations exceed thermal noise sources.

Twice-refocused stimulated echo diffusion imaging: Measuring diffusion time dependence at constant T1 weighting.

PURPOSE: Diffusion times longer than 50 ms are typically probed with stimulated-echo sequences. Varying the diffusion time in stimulated-echo sequences affects the T1 weighting of subcompartments, complicating the analysis of diffusion time dependence. Although inversion recovery preparation could be used to change the T1 weighting, it cannot ensure equal T1 weighting at arbitrary mixing times. In this article, a sequence that ensures constant T1 weighting over a wide range of diffusion times is presented. METHODS: The proposed sequence features 2 independent longitudinal storage periods: TM1 and TM2 . Diffusion encoding is performed during TM1 , effectively coupling the diffusion time and TM1 . Equal T1 weighting at arbitrary diffusion times is realized by keeping the total mixing time TM1 + TM2 constant. The sequence was compared with conventional stimulated-echo measurements of diffusion in a 2-compartment phantom consisting of distilled water and paraffinum perliquidum. Additionally, in vivo DTI of the brain was carried out for 8 healthy volunteers with diffusion times ranging from 50 to 500 ms. RESULTS: Diffusion time dependence of the axial and radial diffusivity was detected in the brain. Both sequences resulted in almost identical diffusivities in white matter. In regions containing partial volumes of gray and white matter, a dependency on T1 weighting was observed. CONCLUSION: In accordance with previous studies, little variance of T1 values appeared to be present in healthy white matter. However, this is likely different in diseased tissue. Here, the proposed sequence can be effective in differentiating between diffusion time dependence and T1 weighting effects.

Transverse relaxometry with transmit field-constrained stimulated echo compensation.

OBJECTIVE: Purely exponential decay is rarely observed in conventional mono-exponential T2 mapping due to transmit field inhomogeneity and calibration errors, which collectively introduce stimulated and indirect echo pathways. Stimulated echo correction (SEC) requires an additional fit parameter for the transmit field, resulting in greater uncertainty in T2 relative to mono-exponential fitting. The aim of this study was to develop an accurate and precise method for T2 mapping using SEC. METHODS: The proposed method, called two-step SEC (tSEC), leverages spatial correlations in the transmit field to reduce the number of fully independent fitting parameters from three to two. The method involves a two-pass fit: the first pass involves a fast but standard SEC fit. The initially estimated transmit field is smoothed and provided as a fixed input to the second pass. RESULTS: Simulations and in vivo experiments demonstrated up to 38% and 27% decreases in relative T2 variance with tSEC relative to SEC. Average T2 values were unchanged between tSEC and SEC fits. The proposed method uses the same input data as SEC and exponential fits, so it is applicable to existing data. DISCUSSION: The proposed method generates reliable and reproducible quantitative T2 maps and should be considered for future relaxometry studies.

The quest for high spatial resolution diffusion-weighted imaging of the human brain in vivo.

Diffusion-weighted imaging, a contrast unique to MRI, is used for assessment of tissue microstructure in vivo. However, this exquisite sensitivity to finer scales far above imaging resolution comes at the cost of vulnerability to errors caused by sources of motion other than diffusion motion. Addressing the issue of motion has traditionally limited diffusion-weighted imaging to a few acquisition techniques and, as a consequence, to poorer spatial resolution than other MRI applications. Advances in MRI imaging methodology have allowed diffusion-weighted MRI to push to ever higher spatial resolution. In this review we focus on the pulse sequences and associated techniques under development that have pushed the limits of image quality and spatial resolution in diffusion-weighted MRI.

Improved stimulated echo in diffusion magnetic resonance imaging: introducing a π pulse for SNR enhancement.

PURPOSE: Anomalous diffusion in biological tissues can be examined by diffusion MRI for various applications, including tumor diagnosis and measurement of brain fiber pathways. However, the measurement of anomalous diffusion requires high b-values for the diffusion gradient in MRI, and current MRI methods cannot provide a high SNR. This study aimed to improve on the standard stimulated echo (STE) to enhance the SNR in diffusion MRI with high b-values. METHODS: Because of hardware limitations and human safety considerations, prolonging the diffusion time (Δ) is 1 of the few methods available to realize high b-values. Here, we propose a new echo mechanism for diffusion MRI to enhance SNRs under long Δ. By introducing a π pulse at the midpoint between 2nd and 3rd π/2 pulses of STE, we refocus the magnetic moment vectors in the longitudinal plane before the third π/2 pulse is applied, which preserves the full echo signals. This sequence was compared with STE and spin echo (SE). Nine Δs were tested in a phantom. Multi b-values with 2 Δs were tested in a mouse liver, brain, and tumor. RESULTS: Compared with STE and SE, the proposed improved STE (ISTE) exhibited an improved SNR in the phantom experiment and improved performance in the in vivo experiments. CONCLUSION: By using the proposed echo mechanism in diffusion MRI, we enhanced the SNR of the images, which enables us to investigate diffusion behavior at higher b-values and further facilitates the development of quantitative diffusion MRI and radiomics.