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PURPOSE: To compare the performance of multi-echo (ME) and time-division multiplexing (TDM) sequences for accelerated relaxation-diffusion MRI (rdMRI) acquisition and to examine their reliability in estimating accurate rdMRI microstructure measures. METHOD: The ME, TDM, and the reference single-echo (SE) sequences with six TEs were implemented using Pulseq with single-band (SB) and multi-band 2 (MB2) acceleration factors. On a diffusion phantom, the image intensities of the three sequences were compared, and the differences were quantified using the normalized RMS error (NRMSE). Shinnar-Le Roux (SLR) pulses were implemented for the SB-ME and SB-SE sequences to investigate the impact of slice profiles on ME sequences. For the in-vivo brain scan, besides the image intensity comparison and T2-estimates, different methods were used to assess sequence-related effects on microstructure estimation, including the relaxation diffusion imaging moment (REDIM) and the maximum-entropy relaxation diffusion distribution (MaxEnt-RDD). RESULTS: TDM performance was similar to the gold standard SE acquisition, whereas ME showed greater biases (3-4× larger NRMSEs for phantom, 2× for in-vivo). T2 values obtained from TDM closely matched SE, whereas ME sequences underestimated the T2 relaxation time. TDM provided similar diffusion and relaxation parameters as SE using REDIM, whereas SB-ME exhibited a 60% larger bias in the map and on average 3.5× larger bias in the covariance between relaxation-diffusion coefficients. CONCLUSION: Our analysis demonstrates that TDM provides a more accurate estimation of relaxation-diffusion measurements while accelerating the acquisitions by a factor of 2 to 3.

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Purpose: To compare the performance of multi-echo (ME) and time-division multiplexing (TDM) sequences for accelerated relaxation-diffusion MRI (rdMRI) acquisition and to examine their reliability in estimating accurate rdMRI microstructure measures. Method: The ME, TDM, and the reference single-echo (SE) sequences with six echo times (TE) were implemented using Pulseq with single-band (SB-) and multi-band 2 (MB2-) acceleration factors. On a diffusion phantom, the image intensities of the three sequences were compared, and the differences were quantified using the normalized root mean squared error (NRMSE). For the in-vivo brain scan, besides the image intensity comparison and T2-estimates, different methods were used to assess sequence-related effects on microstructure estimation, including the relaxation diffusion imaging moment (REDIM) and the maximum-entropy relaxation diffusion distribution (MaxEnt-RDD). Results: TDM performance was similar to the gold standard SE acquisition, whereas ME showed greater biases (3-4× larger NRMSEs for phantom, 2× for in-vivo). T2 values obtained from TDM closely matched SE, whereas ME sequences underestimated the T2 relaxation time. TDM provided similar diffusion and relaxation parameters as SE using REDIM, whereas SB-ME exhibited a 60% larger bias in the map and on average 3.5× larger bias in the covariance between relaxation-diffusion coefficients. Conclusion: Our analysis demonstrates that TDM provides a more accurate estimation of relaxation-diffusion measurements while accelerating the acquisitions by a factor of 2 to 3.

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PURPOSE: To reduce the inter-scanner variability of diffusion MRI (dMRI) measures between scanners from different vendors by developing a vendor-neutral dMRI pulse sequence using the open-source vendor-agnostic Pulseq platform. METHODS: We implemented a standard EPI based dMRI sequence in Pulseq. We tested it on two clinical scanners from different vendors (Siemens Prisma and GE Premier), systematically evaluating and comparing the within- and inter-scanner variability across the vendors, using both the vendor-provided and Pulseq dMRI sequences. Assessments covered both a diffusion phantom and three human subjects, using standard error (SE) and Lin's concordance correlation to measure the repeatability and reproducibility of standard DTI metrics including fractional anisotropy (FA) and mean diffusivity (MD). RESULTS: Identical dMRI sequences were executed on both scanners using Pulseq. On the phantom, the Pulseq sequence showed more than a 2.5× reduction in SE (variability) across Siemens and GE scanners. Furthermore, Pulseq sequences exhibited markedly reduced SE in-vivo, maintaining scan-rescan repeatability while delivering lower variability in FA and MD (more than 50% reduction in cortical/subcortical regions) compared to vendor-provided sequences. CONCLUSION: The Pulseq diffusion sequence reduces the cross-scanner variability for both phantom and in-vivo data, which will benefit multi-center neuroimaging studies and improve the reproducibility of neuroimaging studies.

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PURPOSE: To develop an open-source prototype of myocardial T1 mapping (Open-MOLLI) to improve accessibility to cardiac T1 mapping and evaluate its repeatability. With Open-MOLLI, we aim to enable faster implementation and testing of sequence modifications and to facilitate inter-scanner and cross-vendor reproducibility studies. METHODS: Open-MOLLI is an inversion-recovery sequence using a balanced SSFP (bSSFP) readout, with inversion and triggering schemes based on the 5(3)3 MOLLI sequence, developed in Pulseq. Open-MOLLI and MOLLI sequences were acquired in the ISMRM/NIST phantom and 21 healthy volunteers. In 18 of those subjects, Open-MOLLI and MOLLI were repeated in the same session (test-retest). RESULTS: Phantom T1 values were comparable between methods, specifically for the vial with reference T1 value most similar to healthy myocardium T1 (T1vial3 = 1027 ms): T1MOLLI = 1011 ± 24 ms versus T1Open-MOLLI = 1009 ± 20 ms. In vivo T1 estimates were similar between Open-MOLLI and MOLLI (T1MOLLI = 1004 ± 33 ms vs. T1Open-MOLLI = 998 ± 52 ms), with a mean difference of -17 ms (p = 0.20), despite noisier Open-MOLLI weighted images and maps. Repeatability measures were slightly higher for Open-MOLLI (RCMOLLI = 3.0% vs. RCOpen-MOLLI = 4.4%). CONCLUSION: The open-source sequence Open-MOLLI can be used for T1 mapping in vivo with similar mean T1 values to the MOLLI method. Open-MOLLI increases the accessibility to cardiac T1 mapping, providing also a base sequence to which further improvements can easily be added and tested.

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PURPOSE: To develop a flexible, vendor-neutral EPI sequence for hyperpolarized 13C metabolic imaging. METHODS: An open-source EPI sequence consisting of a metabolite-specific spectral-spatial RF excitation pulse and a customizable EPI readout was created using the Pulseq framework. To explore the flexibility of our sequence, we tested several versions of the sequence including a symmetric 3D readout with different spatial resolutions for each metabolite (1.0 cm3 and 1.5 cm3). A multichamber phantom constructed with a Shepp-Logan geometry, containing two chambers filled with either natural abundance 13C compounds or hyperpolarized (HP) [1-13C]pyruvate, was used to test each sequence. For experiments involving HP [1-13C]pyruvate, a single chamber was prefilled with nicotinamide adenine dinucleotide hydride and lactate dehydrogenase to facilitate the conversion of [1-13C]pyruvate to [1-13C]lactate. All experiments were performed on a Siemens Prisma 3T scanner. RESULTS: All the sequence variations localized natural-abundance 13C ethylene glycol and methanol to the appropriate compartment of the multichamber phantom. [1-13C]pyruvate was detectable in both chambers following the injection of HP [1-13C]pyruvate, whereas [1-13C]lactate was only found in the chamber containing nicotinamide adenine dinucleotide hydride and lactate dehydrogenase. The conversion rate from [1-13C]pyruvate to [1-13C]lactate (kPL) was 0.01 s-1 (95% confidence interval [0.00, 0.02]). CONCLUSION: We have developed and tested a vendor-neutral EPI sequence for imaging HP 13C agents. We have made all of our sequence creation and image reconstruction code freely available online for other investigators to use.

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PURPOSE: Clinical scanners require pulsed CEST sequences to maintain amplifier and specific absorption rate limits. During off-resonant RF irradiation and interpulse delay, the magnetization can accumulate specific relative phases within the pulse train. In this work, we show that these phases are important to consider, as they can lead to unexpected artifacts when no interpulse gradient spoiling is performed during the saturation train. METHODS: We investigated sideband artifacts using a CEST-3D snapshot gradient-echo sequence at 3 T. Initially, Bloch-McConnell simulations were carried out with Pulseq-CEST, while measurements were performed in vitro and in vivo. RESULTS: Sidebands can be hidden in Z-spectra, and their structure becomes clearly visible only at high sampling. Sidebands are further influenced by B0 inhomogeneities and the RF phase cycling within the pulse train. In vivo, sidebands are mostly visible in liquid compartments such as CSF. Multi-pulse sidebands can be suppressed by interpulse gradient spoiling. CONCLUSION: We provide new insights into sidebands occurring in pulsed CEST experiments and show that, similar as in imaging sequences, gradient and RF spoiling play an important role. Gradient spoiling avoids misinterpretations of sidebands as CEST effects especially in liquid environments including pathological tissue or for CEST resonances close to water. It is recommended to simulate pulsed CEST sequences in advance to avoid artifacts.

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PURPOSE: To develop, optimize, and implement a single shot spiral turbo spin echo (TSE) sequence at 3T and to demonstrate its feasibility to acquire artifact free images of the central nervous system with 1 mm spatial resolution in <200 ms. THEORY AND METHODS: Spiral TSE sequences with annulated spiral segmentation have been implemented with different acquisition modes. In fixed mode, the duration of each spiral segment is fixed to fill the available acquisition time tacq . In tangential mode, the beginning of each spiral segment is reached via a straight tangential trajectory. Tangential mode allows faster transition and thus longer tacq for a given echo spacing (ESP), but less data points can be acquired per acquisition interval. Alternating between spiral-in and spiral-out readout in alternating echoes leads to a somewhat different point spread function for off-resonant spins. RESULTS: Images of the brain with 1 mm spatial resolution acquired with a variable density spiral with ∼40% undersampling can be acquired in a single shot. All acquisition modes produce comparable image quality. Only mild artifacts in regions of strong susceptibility effects can be observed for ESP of 10 ms and below. The use of variable flip angle schemes allows seamless acquisition of consecutive slices and/or dynamic scans without waiting time between consecutive acquisitions. Comparison with images acquired at 1.5T shows reduced susceptibility artifacts within the brain and facial structures. CONCLUSION: Single shot spiral TSE has been demonstrated to enable highly efficient acquisition of high-resolution images of the brain in <200 ms per slice.

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PURPOSE: As the field of CEST grows, various novel preparation periods using different parameters are being introduced. At the same time, large, multisite clinical studies require clearly defined protocols, especially across different vendors. Here, we propose a CEST definition standard using the open Pulseq format for a shareable, simple, and exact definition of CEST protocols. METHODS: We present the benefits of such a standard in three ways: (1) an open database on GitHub, where fully defined, human-readable CEST protocols can be shared; (2) an open-source Bloch-McConnell simulation to test and optimize CEST preparation periods in silico; and (3) a hybrid MR sequence that plays out the CEST preparation period and can be combined with any existing readout module. RESULTS: The exact definition of the CEST preparation period, in combination with the flexible simulation, leads to a good match between simulations and measurements. The standard allowed finding consensus on three amide proton transfer-weighted protocols that could be compared in healthy subjects and a tumor patient. In addition, we could show coherent multisite results for a sophisticated CEST method, highlighting the benefits regarding protocol sharing and reproducibility. CONCLUSION: With Pulseq-CEST, we provide a straightforward approach to standardize, share, simulate, and measure different CEST preparation schemes, which are inherently completely defined.

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PURPOSE: To provide a single open-source platform for comprehensive MR algorithm development inclusive of simulations, pulse sequence design and deployment, reconstruction, and image analysis. METHODS: We integrated the "Pulseq" platform for vendor-independent pulse programming with Graphical Programming Interface (GPI), a scientific development environment based on Python. Our integrated platform, Pulseq-GPI, permits sequences to be defined visually and exported to the Pulseq file format for execution on an MR scanner. For comparison, Pulseq files using either MATLAB only ("MATLAB-Pulseq") or Python only ("Python-Pulseq") were generated. We demonstrated three fundamental sequences on a 1.5 T scanner. Execution times of the three variants of implementation were compared on two operating systems. RESULTS: In vitro phantom images indicate equivalence with the vendor supplied implementations and MATLAB-Pulseq. The examples demonstrated in this work illustrate the unifying capability of Pulseq-GPI. The execution times of all the three implementations were fast (a few seconds). The software is capable of user-interface based development and/or command line programming. CONCLUSION: The tool demonstrated here, Pulseq-GPI, integrates the open-source simulation, reconstruction and analysis capabilities of GPI Lab with the pulse sequence design and deployment features of Pulseq. Current and future work includes providing an ISMRMRD interface and incorporating Specific Absorption Ratio and Peripheral Nerve Stimulation computations.

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PURPOSE: Implementing new magnetic resonance experiments, or sequences, often involves extensive programming on vendor-specific platforms, which can be time consuming and costly. This situation is exacerbated when research sequences need to be implemented on several platforms simultaneously, for example, at different field strengths. This work presents an alternative programming environment that is hardware-independent, open-source, and promotes rapid sequence prototyping. METHODS: A novel file format is described to efficiently store the hardware events and timing information required for an MR pulse sequence. Platform-dependent interpreter modules convert the file to appropriate instructions to run the sequence on MR hardware. Sequences can be designed in high-level languages, such as MATLAB, or with a graphical interface. Spin physics simulation tools are incorporated into the framework, allowing for comparison between real and virtual experiments. RESULTS: Minimal effort is required to implement relatively advanced sequences using the tools provided. Sequences are executed on three different MR platforms, demonstrating the flexibility of the approach. CONCLUSION: A high-level, flexible and hardware-independent approach to sequence programming is ideal for the rapid development of new sequences. The framework is currently not suitable for large patient studies or routine scanning although this would be possible with deeper integration into existing workflows. Magn Reson Med 77:1544-1552, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

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