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► Lorentzian-shaped 3-pool-model function for z-spectra. ► Range of spillover influence by FWHM evaluation of direct water saturation. ► Determination of MT and CEST effect without ...further knowledge of the system. ► Scope of practical application estimated by Monte-Carlo simulation: moderate
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1, high SNR, and high sampling rate.
Chemical exchange saturation transfer (CEST) processes in aqueous systems are quantified by evaluation of z-spectra, which are obtained by acquisition of the water proton signal after selective RF presaturation at different frequencies. When saturation experiments are performed
in vivo, three effects are contributing: CEST, direct water saturation (spillover), and magnetization transfer (MT) mediated by protons bound to macromolecules and bulk water molecules. To analyze the combined saturation a new analytical model is introduced which is based on the weak-saturation-pulse (WSP) approximation. The model combines three single WSP approaches to a general model function. Simulations demonstrated the benefits and constraints of the model, in particular the capability of the model to reproduce the ideal proton transfer rate (PTR) and the conventional MT rate for moderate spillover effects (up to 50% direct saturation at CEST-resonant irradiation). The method offers access to PTR from z-spectra data without further knowledge of the system, but requires precise measurements with dense saturation frequency sampling of z-spectra. PTR is related to physical parameters such as concentration, transfer rates and thereby pH or temperature of tissue, using either exogenous contrast agents (PARACEST, DIACEST) or endogenous agents such as amide protons and –OH protons of small metabolites.
Magnetic resonance imaging and spectroscopic techniques are widely used in humans both for clinical diagnostic applications and in basic research areas such as cognitive neuroimaging. In recent ...years, new human MR systems have become available operating at static magnetic fields of 7 T or higher (≥300 MHz proton frequency). Imaging human-sized objects at such high frequencies presents several challenges including non-uniform radiofrequency fields, enhanced susceptibility artifacts, and higher radiofrequency energy deposition in the tissue. On the other side of the scale are gains in signal-to-noise or contrast-to-noise ratio that allow finer structures to be visualized and smaller physiological effects to be detected. This review presents an overview of some of the latest methodological developments in human ultra-high field MRI/MRS as well as associated clinical and scientific applications. Emphasis is given to techniques that particularly benefit from the changing physical characteristics at high magnetic fields, including susceptibility-weighted imaging and phase-contrast techniques, imaging with X-nuclei, MR spectroscopy, CEST imaging, as well as functional MRI. In addition, more general methodological developments such as parallel transmission and motion correction will be discussed that are required to leverage the full potential of higher magnetic fields, and an overview of relevant physiological considerations of human high magnetic field exposure is provided.
Purpose
Chemical exchange saturation transfer MRI can provide accurate pH images, but the slow scan time (due to long saturation periods and multiple offsets sampling) reduce both the volume coverage ...and spatial resolution capability, hence the possibility to interrogate the heterogeneity in tumors and organs. To overcome these limitations, we propose a fast multislice CEST‐MRI sequence with high pH accuracy and spatial resolution.
Methods
The sequence first uses a long saturation pulse to induce the steady‐state CEST contrast and a second short saturation pulse repeated after each image acquisition to compensate for signal losses based on an uneven irradiation scheme combined with a single‐shot rapid acquisition with refocusing echoes readout. Sequence sensitivity and accuracy in measuring pH was optimized by simulation and assessed by in vitro studies in pH‐varying phantoms. In vivo validation was performed in two applications by acquiring multislice pH images covering the whole tumors and kidneys after iopamidol injection.
Results
Simulated and in vivo data showed comparable contrast efficiency and pH responsiveness by reducing saturation time. The experimental data from a homogeneous, pH‐varying, iopamidol‐containing phantom show that the sequence produced a uniform CEST contrast across slices and accurate values across slices in less than 10 minutes. In vivo measurements allowed us to quantify the 3D pH gradients of tumors and kidneys, with pH ranges comparable with the literature.
Conclusion
The proposed fast multislice CEST‐MRI sequence allows volumetric acquisitions with good pH sensitivity, accuracy, and spatial resolution for several in vivo pH imaging applications.
Amide proton transfer‐weighted (APTw) MR imaging shows promise as a biomarker of brain tumor status. Currently used APTw MRI pulse sequences and protocols vary substantially among different ...institutes, and there are no agreed‐on standards in the imaging community. Therefore, the results acquired from different research centers are difficult to compare, which hampers uniform clinical application and interpretation. This paper reviews current clinical APTw imaging approaches and provides a rationale for optimized APTw brain tumor imaging at 3 T, including specific recommendations for pulse sequences, acquisition protocols, and data processing methods. We expect that these consensus recommendations will become the first broadly accepted guidelines for APTw imaging of brain tumors on 3 T MRI systems from different vendors. This will allow more medical centers to use the same or comparable APTw MRI techniques for the detection, characterization, and monitoring of brain tumors, enabling multi‐center trials in larger patient cohorts and, ultimately, routine clinical use.
Purpose
CEST MRI enables imaging of distributions of low‐concentrated metabolites as well as proteins and peptides and their alterations in diseases. CEST examinations often suffer from low spatial ...resolution, long acquisition times, and concomitant motion artifacts. This work aims to maximize both resolution and volume coverage with a 3D‐EPI snapshot CEST approach at 3T, allowing for fast and robust whole‐brain CEST MRI.
Methods
Resolution and temporal SNR of 3D‐EPI examinations with nonselective excitation were optimized at a clinical 3T MR scanner in five healthy subjects using a clinical head/neck coil. A CEST presaturation module for low power relayed nuclear Overhauser enhancement and amide proton transfer contrast was applied as an example. The suggested postprocessing included motion correction, dynamic B0 correction, denoising, and B1 correction and was compared to an established 3D‐gradient echo‐based sequence.
Results
CEST examinations were performed at 1.8 mm nominal isotropic resolution in 4.3 s per presaturation offset. In contrast to slab‐selective 3D or multislice approaches, the whole brain was covered. Repeated examinations at three different B1 values took 13 minutes for 58 presaturation offsets with temporal SNR around 75. The resulting CEST effects revealed significant gray and white matter contrast and were of similar quality across the whole brain. Coefficient of variation across three healthy subjects was below 9%.
Conclusion
The suggested protocol enables whole brain coverage at 1.8 mm isotropic resolution and fast acquisition of 4.3 s per presaturation offset. For the fitted CEST amplitudes, high reproducibility was proven, increasing the opportunities of quantitative CEST investigations at 3T significantly.
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.