Single-shot multi-b-value (SSMb) diffusion-weighted MRI using spin echo and stimulated echoes with variable flip angles.

Conventional diffusion-weighted imaging (DWI) sequences employing a spin echo or stimulated echo sensitize diffusion with a specific b-value at a fixed diffusion direction and diffusion time (Δ). To compute apparent diffusion coefficient (ADC) and other diffusion parameters, the sequence needs to be repeated multiple times by varying the b-value and/or gradient direction. In this study, we developed a single-shot multi-b-value (SSMb) diffusion MRI technique, which combines a spin echo and a train of stimulated echoes produced with variable flip angles. The method involves a pair of 90° radio frequency (RF) pulses that straddle a diffusion gradient lobe (GD), to rephase the magnetization in the transverse plane, producing a diffusion-weighted spin echo acquired by the first echo-planar imaging (EPI) readout train. The magnetization stored along the longitudinal axis is successively re-excited by a series of n variable-flip-angle pulses, each followed by a diffusion gradient lobe GD and a subsequent EPI readout train to sample n stimulated-echo signals. As such, (n + 1) diffusion-weighted images, each with a distinct b-value, are acquired in a single shot. The SSMb sequence was demonstrated on a diffusion phantom and healthy human brain to produce diffusion-weighted images, which were quantitative analyzed using a mono-exponential model. In the phantom experiment, SSMb provided similar ADC values to those from a commercial spin-echo EPI (SE-EPI) sequence (r = 0.999). In the human brain experiment, SSMb enabled a fourfold scan time reduction and yielded slightly lower ADC values (0.83 ± 0.26 µm2/ms) than SE-EPI (0.88 ± 0.29 µm2/ms) in all voxels excluding cerebrospinal fluid, likely due to the influence of varying diffusion times. The feasibility of using SSMb to acquire multiple images in a single shot for intravoxel incoherent motion (IVIM) analysis was also demonstrated. In conclusion, despite a relatively low signal-to-noise ratio, the proposed SSMb technique can substantially increase the data acquisition efficiency in DWI studies.

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.

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.

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.

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.

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.

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).

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.

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.

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.

Stimulated echo based mapping (STEM) of T1 , T2 , and apparent diffusion coefficient: validation and protocol optimization.

PURPOSE: To present a stimulated-echo based mapping (STEM) approach for simultaneous T1 , T2 , and ADC mapping. METHODS: Diffusion-weighted stimulated-echo images with various combinations of mixing time (TM), TE, and b-value were acquired to enable simultaneous mapping of T1 , T2 , and ADC. The proposed STEM method was performed by densely sampling the TM-TE-b space in a phantom and in brain and prostate of healthy volunteers. T1 , T2 , and ADC from STEM were compared to reference mapping methods. Additionally, protocol optimization was performed to enable rapid STEM acquisition within 2 min by sparsely sampling the TM-TE-b space. The T1 , T2 , and ADC measurements from rapid acquisitions were compared to the densely sampled STEM for evaluation. Finally, a patient with biopsy-proven high-risk prostate cancer was imaged to demonstrate the ability of STEM to differentiate cancer and healthy tissues. RESULTS: Relative to the reference measurements, densely sampled STEM provided accurate quantitative T1 , T2 , and ADC mapping in phantoms (R2 = 0.999, slope between 0.97-1.03), as well as in brain and prostate. Further, the T1 , T2 , and ADC measurements from the optimized rapid STEM acquisitions agreed closely with densely sampled STEM. Finally, STEM showed decreased T2 and ADC in prostate cancer compared to healthy prostate tissue. CONCLUSION: STEM provides accurate simultaneous mapping of T1 , T2 , and ADC. This method may enable rapid and accurate multi-parametric tissue characterization for clinical and research applications.

Three-dimensional diffusion imaging with spiral encoded navigators from stimulated echoes (3D-DISPENSE).

PURPOSE: To introduce a new method for motion-insensitive 3D multishot diffusion imaging using 3D spiral-encoded navigators from stimulated echoes (3D-DISPENSE). METHODS: The 3D-DISPENSE sequence contains a 3D stack-of-spiral navigator generated between the diffusion preparation and the turbo spin-echo image acquisition from the twin pathway of a stimulated echo. Unlike normal navigator methods, 3D-DISPENSE separates the navigator acquisition from the imaging readout without compromising the image SNR. Phase information from the navigators was included in an iterative image reconstruction algorithm to correct for intershot phase incoherence caused by motion. RESULTS: In a phantom experiment, 3D-DISPENSE correctly estimated deliberately introduced phase errors. In a moving phantom, motion-induced artifacts in the DWI were greatly mitigated by 3D-DISPENSE. The ADC after 3D-DISPENSE correction was identical to the reference. In a brain diffusion tensor experiment, phase-incoherence artifacts from breathing, cardiac, and subject motion were removed almost perfectly in all view angles, resulting in distortion-free DWI and color-coded fractional anisotropy maps with 1.5-mm isotropic resolution and nearly full brain coverage. CONCLUSION: Three-dimensional DISPENSE corrects motion-induced phase-incoherence artifacts in 3D multishot diffusion imaging and produces high-quality 3D DWI and DTI.

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.

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.

Diffusion tensor imaging of human Achilles tendon by stimulated echo readout-segmented EPI (ste-RS-EPI).

PURPOSE: Healing, regeneration, and remodeling of the injured Achilles tendon are associated with notable changes in tendon architecture. However, assessing Achilles microstructural properties with conventional diffusion tension imaging (DTI) remains a challenge because of very short T2 / T 2 * values of the tendon. Hence, the objective of this study was to develop a novel Achilles tendon DTI protocol for a non-invasive investigation of the changes of microstructural integrity in tendinopathy. METHODS: A novel stimulated echo readout-segmented EPI (ste-RS-EPI) DTI sequence was proposed to achieve a TE of ∼14-20 ms for typical b-values of 400-800 s/mm2 on clinical 3T MRI scanners. To further boost tendon MR signal, the Achilles was positioned at the magic angle (∼55 °) with respect to the scanner B0 field. The sensitivity of the developed protocol was evaluated in 19 healthy participants and 6 patients with clinically confirmed tendinopathy. RESULTS: Compared to spin echo RS-EPI DTI protocol, ste-RS-EPI provided an ∼100-200% increase in Achilles MR signal. Tendinopathic Achilles demonstrated a high degree of microstructural disruption based on DTI tractography analysis, with significantly lower (P < 0.05) axial diffusivity (1.20 ± 0.19 vs. 1.39 ± 0.10 × 10-3 mm2 /s), radial diffusivity (0.72 ± 0.11 vs. 0.81 ± 0.08 × 10-3 mm2 /s), and mean diffusivity (0.87 ± 0.14 vs. 1.00 ± 0.07 × 10-3 mm2 /s), but no significant difference in fractional anisotropy (0.38 ± 0.04 vs. 0.38 ± 0.05; P = 0.86). CONCLUSION: Achilles tendon ste-RS-EPI DTI can non-invasively detect the tendinopathy-induced changes to microstructural integrity, consistent with the disruption of collagen arrangement and increased cellularity. This study demonstrated the robustness and sensitivity of the proposed protocol in Achilles tendinopathy.

Choice of reference measurements affects quantification of long diffusion time behaviour using stimulated echoes.

PURPOSE: To demonstrate how reference data affect the quantification of the apparent diffusion coefficient (ADC) in long diffusion time measurements with diffusion-weighted stimulated echo acquisition mode (DW-STEAM) measurements, and to present a modification to avoid contribution from crusher gradients in DW-STEAM. METHODS: For DW-STEAM, reference measurements at long diffusion times have significant b0 value, because b = 0 cannot be achieved in practice as a result of the need for signal spoiling. Two strategies for acquiring reference data over a range of diffusion times were considered: constant diffusion weighting (fixed-b0 ) and constant gradient area (fixed-q0 ). Fixed-b0 and fixed-q0 were compared using signal calculations for systems with one and two diffusion coefficients, and experimentally using data from postmortem human corpus callosum samples. RESULTS: Calculations of biexponential diffusion decay show that the ADC is underestimated for reference images with b > 0, which can induce an apparent time-dependence for fixed-q0 . Restricted systems were also found to be affected. Experimentally, the exaggeration of the diffusion time-dependent effect under fixed-q0 versus fixed-b0 was in a range predicted theoretically, accounting for 62% (longitudinal) and 35% (radial) of the time dependence observed in white matter. CONCLUSIONS: Variation in the b-value of reference measurements in DW-STEAM can induce artificial diffusion time dependence in ADC, even in the absence of restriction. Magn Reson Med 79:952-959, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Accelerated radial diffusion spectrum imaging using a multi-echo stimulated echo diffusion sequence.

PURPOSE: Diffusion spectrum imaging (DSI) provides us non-invasively and robustly with anatomical details of brain microstructure. To achieve sufficient angular resolution, DSI requires a large number of q-space samples, leading to long acquisition times. This need is mitigated here by combining the beneficial properties of Radial q-space sampling for DSI with a Multi-Echo Stimulated Echo Sequence (MESTIM). METHODS: Full 2D k-spaces for each of several q-space samples, along the same radially outward line in q-space, are acquired in one readout train with one spin and three stimulated echoes. RF flip angles are carefully chosen to distribute spin magnetization over the echoes and the DSI reconstruction is adapted to account for differences in diffusion time among echoes. RESULTS: Individual datasets and bootstrapped reproducibility analysis demonstrate image quality and SNR of the more-than-twofold-accelerated RDSI MESTIM sequence. Orientation distribution functions (ODF) and tractography results benefit from the longer diffusion times of the latter echoes in the echo train. CONCLUSION: A MESTIM sequence can be used to shorten RDSI acquisition times significantly without loss of image or ODF quality. Further acceleration is possible by combination with simultaneous multi-slice techniques. Magn Reson Med 79:306-316, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Limitations of skipping echoes for exponential T2 fitting.

BACKGROUND: Exponential fitting of multiecho spin echo sequences with skipped echoes is still commonly used for quantification of transverse relaxation (T2 ). PURPOSE: To examine the efficacy of skipped echo methods for T2 quantification against computational modeling of the exact signal decay. STUDY TYPE: Prospective comparison of methods. SUBJECTS/PHANTOM: Eight volunteers were imaged at 4.7T, six volunteers at 1.5T, and phantoms ([MnCl2 ] = 68-270 mM). FIELD STRENGTH/SEQUENCE: 1.5T and 4.7T; multiple-echo spin echo. ASSESSMENT: Exponential fitting for T2 using all echoes, skipping the first echo or skipping all odd echoes, compared with Bloch simulations. Resulting T2 values were examined over a range of T2 (10-150 msec), refocusing flip angles (90-270°), and echo train lengths (ETL = 6-32). STATISTICAL TESTS: Shapiro-Wilk tests and Q-Q plots were used to check for normality of data. Paired sample t-tests and Wilcoxon rank tests were used to compare fitting models using α = 0.05. Multiple comparisons were accounted for with Bonferroni correction. RESULTS: In examined regions of interest, typical incorrect estimation of T2 ranged from 23-39% for exponential fitting of all echoes, or 15-32% for skipped echo methods. In vivo, T2 estimation error was reduced to as little as 10% with skipped echo methods using 180° refocusing and ETL = 8, although error varied due to refocusing angle, T2 , and ETL. In vivo, skipped echo T2 values were significantly different than all echo exponential fitting (P < 0.004), but also were significantly different from reference values (P < 0.002, except frontal white matter). Simulations showed skipping the first echo was the most effective form of exponential fitting, in particular for T2 <50 msec and ETL = 8, with potential to reduce T2 errors to 10%, depending on refocusing angle and T2 . DATA CONCLUSION: Skipping echoes is insufficient for avoiding stimulated echo contamination. Resulting T2 errors depend on a complicated interplay of T2 , refocusing angle, and ETL. Modeling of the multiecho sequence is recommended. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1432-1440.

Intravoxel incoherent motion (IVIM) imaging in human achilles tendon.

BACKGROUND: Limited microcirculation has been implicated in Achilles tendinopathy and may affect healing and disease progression. Existing invasive and noninvasive approaches to evaluate tendon microcirculation lack sensitivity and spatial coverage. PURPOSE: To develop a novel Achilles tendon intravoxel incoherent motion (IVIM) MRI protocol to overcome the limitations from low tendon T2 /T2 * value and low intratendinous blood volume and blood velocity to evaluate tendon microcirculation. STUDY TYPE: Prospective. SUBJECTS: Sixteen healthy male participants (age 31.0 ± 2.1) were recruited. FIELD STRENGTH/SEQUENCE: A stimulated echo readout-segmented echo planar imaging (ste-RS-EPI) IVIM sequence at 3.0T. ASSESSMENT: The feasibility of the proposed ste-RS-EPI IVIM protocol combined with Achilles tendon magic angle effect was evaluated. The sensitivity of the protocol was assessed by an exercise-induced intratendinous hemodynamic response in healthy participants. The vascular origin of the observed IVIM signal was validated by varying the diffusion mixing time and echo time. STATISTICAL TESTS: Two-tailed t-tests were used to evaluate differences (P < 0.05 was considered significant). RESULTS: Consistent with known tendon hypovascularity, the midportion Achilles tendon at baseline showed significantly lower IVIM-derived perfusion fraction (fp ) (3.1 ± 0.9%) compared to the proximal and distal Achilles tendon (6.0 ± 1.8% and 6.1 ± 2.0%, respectively; P < 0.01). Similarly, the midportion Achilles tendon exhibited significantly lower baseline blood flow index (D*×fp ) (40.9 ± 19.2, 18.3 ± 5.3, and 32.0 ± 9.4 in proximal, midportion, and distal Achilles tendon, respectively; P < 0.01). Eccentric heel-raise exercise led to ∼2 times increase of Achilles tendon blood flow in healthy participants. Consistent with its vascular origin, the estimated fp demonstrated a high dependency to IVIM protocol parameters, while the T1 /T2 -corrected absolute intratendinous microvascular blood volume fraction (Vb ) did not vary. DATA CONCLUSION: Achilles tendon ste-RS-EPI IVIM noninvasively assessed baseline values and exercise-induced changes to tendon microcirculation in healthy tendon. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1690-1699.