Description: Purpose To develop a rapid segmentation-free method to visualize and compute wall shear stress (WSS) throughout the aorta using 4D Flow MRI data. WSS is the drag force-per-area the vessel endothelium exerts on luminal blood; abnormal levels of WSS are associated with cardiovascular pathologies. Previous methods for computing WSS are bottlenecked by labor-intensive manual segmentation of vessel boundaries. A rapid automated segmentation-free method for computing WSS is presented. Theory and Methods Shear stress is the dot-product of the viscous stress tensor and the inward normal vector. The inward normal vectors are approximated as the gradient of fluid speed at every voxel. Subsequently, a 4D map of shear stress is computed as the partial derivatives of velocity with respect to the inward normal vectors. We highlight the shear stress near the wall by fusing visualization with edge-emphasized anatomical data. Results As a proof-of-concept, four cases with aortic pathologies are presented. Visualization allows for rapid localization of pathologic WSS. Subsequent analysis of these pathological regions enables quantification of WSS. Average WSS during peak systole measures approximately 50–60 cPa in nonpathological regions of the aorta and is elevated in regions of stenosis, coarctation, and dissection. WSS is reduced in regions of aneurysm. Conclusion A volumetric technique for calculation and visualization of WSS from 4D Flow MRI data is presented. Traditional labor-intensive methods for WSS rely on explicit manual segmentation of vessel boundaries before visualization. This automated volumetric strategy for visualization and quantification of WSS may facilitate its clinical translation.

Description: Purpose To map the cerebral metabolic rate of oxygen (CMRO 2 ) by estimating the oxygen extraction fraction (OEF) from gradient echo imaging (GRE) using phase and magnitude of the GRE data. Theory and Methods 3D multi-echo gradient echo imaging and perfusion imaging with arterial spin labeling were performed in 11 healthy subjects. CMRO 2 and OEF maps were reconstructed by joint quantitative susceptibility mapping (QSM) to process GRE phases and quantitative blood oxygen level-dependent (qBOLD) modeling to process GRE magnitudes. Comparisons with QSM and qBOLD alone were performed using ROI analysis, paired t-tests, and Bland-Altman plot. Results The average CMRO 2 value in cortical gray matter across subjects were 140.4 ± 14.9, 134.1 ± 12.5, and 184.6 ± 17.9 μmol/100 g/min, with corresponding OEFs of 30.9 ± 3.4%, 30.0 ± 1.8%, and 40.9 ± 2.4% for methods based on QSM, qBOLD, and QSM+qBOLD, respectively. QSM+qBOLD provided the highest CMRO 2 contrast between gray and white matter, more uniform OEF than QSM, and less noisy OEF than qBOLD. Conclusion Quantitative CMRO 2 mapping that fits the entire complex GRE data is feasible by combining QSM analysis of phase and qBOLD analysis of magnitude.

Description: Purpose Magnetic resonance imaging has been used extensively to track in vivo implanted cells that have been previously labeled with relaxation enhancers. However, this approach is not suitable to track multiple cell populations, as it may lead to confounding results in case the contrast agent is released from the labeled cells. This paper demonstrates how the use of CEST agents can overcome these issues. After encapsulating paramagnetic lanthanide shift reagents, we may shift the absorption frequency of the intracellular water resonance (δ In ), thus generating frequency-encoding CEST responsive cells that can be visualized in the MR image by applying the proper RF irradiation. Methods Eu-HPDO3A, Dy-HPDO3A, and Tm-HPDO3A were used as shift reagents for labeling murine breast cancer cells and murine macrophages by hypotonic swelling and pinocytosis. The CEST-MR images were acquired at 7 T, and the saturation transfer effect was measured. Samples at different dilution of cells were analyzed to quantify the detection threshold. In vitro experiments of cell proliferation were carried out. Finally, murine breast cancer cells were injected subcutaneously in mice, and MR images were acquired to assess the proliferation index in vivo. Results It was found that entrapment of the paramagnetic complexes into endosomes (i.e., using the pinocytosis route) leads to an enhanced shift of the intracellular water resonance. δ In appears to be proportional to the effective magnetic moment (μ eff ) and to the concentration of the loaded lanthanide complex. Moreover, a higher shift is present when the complexes are entrapped in the endosomes. The cell proliferation index was assessed both in vitro and in vivo by evaluating the reduction of δ In value in the days after the cell labeling. Conclusion Cells can be visualized by CEST MRI after loading with paramagnetic shift reagent, by exploiting the large ensemble of the properly shifted intracellular water molecules. A better performance is obtained when the complexes are entrapped inside the endosomes. The observed (δ In ) value is strongly correlated to the chemical nature of the probe, and to its concentration and cellular localization. Two applications of this method are reported in this paper: (1) for in vivo cell visualization and (2) for the monitoring of the cellular proliferation process, as this method is accompanied by a change in δ In that may be exploited as a longitudinal reporter of the proliferation rate.

Description: Purpose To develop a real-time dynamic MRI method for comprehensive evaluation of velum movement during speech. Methods Dynamic MRI has been used to study velopharyngeal insufficiency (VPI) by imaging the movement of the velum during speech, because it can provide good anatomic details with no exposed radiation. To be able to comprehensively evaluate dynamic velum movement, a real-time spiral non-balanced SSFP sequence was developed with simultaneous dual-planar coverage and improved spatial and temporal resolution using a combination of parallel imaging and spatial and temporal compressed sensing to achieve 6 × acceleration. New off-resonance correction and post-processing methods were also developed to reduce blurring and slice crosstalk. Results The method demonstrated good image quality for visualizing dynamic velum movement with reduced blurring and improved image homogeneity. Spatial resolution of 1.2*1.2 mm 2 with 150 mm FOV and temporal resolution of 20 frames-per-second with simultaneous dual-planar coverage was achieved. Conclusions This work describes a new technique for studying speech disorders using dual-planar accelerated spiral dynamic MRI.

Description: Purpose To investigate the feasibility of measuring the subtle disruption of blood-brain barrier (BBB) using DCE-MRI with a scan duration shorter than 10 min. Methods The extended Patlak-model (EPM) was introduced to include the effect of plasma flow ( F p ) in the estimation of vascular permeability–surface area product ( PS ). Numerical simulation studies were carried out to investigate how the reduction in scan time affects the accuracy in estimating contrast kinetic parameters. DCE-MRI studies of the rat brain were conducted with Fisher rats to confirm the results from the simulation. Intracranial F98 glioblastoma models were used to assess areas with different levels of permeability. In the normal brain tissues, the Patlak model (PM) and EPM were compared, whereas the 2-compartment-exchange-model (TCM) and EPM were assessed in the peri-tumor and the tumor regions. Results The simulation study results demonstrated that scan time reduction could lead to larger bias in PS estimated by PM (〉2000%) than by EPM (〈47%), especially when F p is low. When F p was high as in the gray matter, the bias in PM- PS (〉900%) were larger than that in EPM- PS (〈42%). The animal study also showed similar results, where the PM parameters were more sensitive to the scan duration than the EPM parameters. It was also demonstrated that, in the peri-tumor region, the EPM parameters showed less change by scan duration than the TCM parameters. Conclusion The results of this study suggest that EPM can be used to measure PS with a scan duration of 10 min or less.

Description: Purpose To develop a new MRI technique to rapidly measure exchange rates in CEST MRI. Methods A novel pulse sequence for measuring chemical exchange rates through a progressive saturation recovery process, called PRO-QUEST (progressive saturation for quantifying exchange rates using saturation times), has been developed. Using this method, the water magnetization is sampled under non-steady-state conditions, and off-resonance saturation is interleaved with the acquisition of images obtained through a Look-Locker type of acquisition. A complete theoretical framework has been set up, and simple equations to obtain the exchange rates have been derived. Results A reduction of scan time from 58 to 16 minutes has been obtained using PRO-QUEST versus the standard QUEST. Maps of both T 1 of water and B 1 can simply be obtained by repetition of the sequence without off-resonance saturation pulses. Simulations and calculated exchange rates from experimental data using amino acids such as glutamate, glutamine, taurine, and alanine were compared and found to be in good agreement. The PRO-QUEST sequence was also applied on healthy and infarcted rats after 24 hours, and revealed that imaging specificity to ischemic acidification during stroke was substantially increased relative to standard amide proton transfer–weighted imaging. Conclusion Because of the reduced scan time and insensitivity to nonchemical exchange factors such as direct water saturation, PRO-QUEST can serve as an excellent alternative for researchers and clinicians interested to map pH changes in vivo.

Description: Purpose To develop a rapid, non-CPMG high-resolution volumetric imaging approach, exhibiting a speed and in-plane resilience to field inhomogeneities comparable to RARE/turbo-spin-echo (TSE) while endowed with unique downsampling characteristics. Methods A multi-scan extension of cross-term spatiotemporal encoding (xSPEN) is introduced and analyzed. The method simultaneously yields k y / k z data containing low and high frequency components, as well as transposed, low-resolution z / y images. This dual k -/spatial-domain information is captured by a multi-scan procedure that phase-encodes k y while simultaneously slice-selecting z . A reconstruction scheme converting this information into high resolution 3D images with fully multiplexed volumetric coverage is introduced and exemplified. Results Phase-encoded xSPEN was tested by human brain imaging at sub-mm resolutions. The method exceeded 2D TSE's sensitivity by factors of ≈3–4, while providing similar resolution and SNR as 3D TSE in ≈50% acquisition times. The method's contrast is dominated by T 2 and is free from “bright-fat” effects associated to spin-echo trains. Further acceleration is enabled by the method's downsampling abilities. Tradeoffs between encoding time, number of measurements, spatial resolution, SNR, and artifact levels are also laid out. Conclusion A new MRI strategy is introduced delivering high in- and through-plane resolutions while enjoying full Fourier multiplexing, leading to fast acquisitions with high SNR.

Description: Purpose To demonstrate a simple head-sized phantom for realistic static and RF field characterization in high field systems. Methods The head-sized phantom was composed of an ellipsoidal compartment and a spherical cavity to mimic the nasal cavity. The phantom was filled with an aqueous solution of polyvinylpyrrolidone (PVP), to mimic the average dielectric properties of brain tissue. The static and RF field distributions were characterized on a 7T MRI system and compared to in vivo measurements and simulations. MR thermometry was performed, and the results were compared to thermal simulations for RF validation purposes. Results Accurate reproduction of both static and RF fields patterns observed in vivo was confirmed experimentally and was shown to be strongly affected by the inclusion of the spherical cavity. MR thermometry and transmit efficiency ( ) measurements were obtained in close agreement with simulations (peak values agreeing within 0.3 °C and 0.02 μT/√W) as well as fiber optic thermal probes (RMSE 〈 0.18 °C). Conclusions A simple head-sized phantom has been presented that produces B 0 and nonuniformities similar to those encountered in the human head and allows for accurate MR thermometry measurements, making this a suitable reference phantom for RF validation and methodological development in high field MRI.

Description: Purpose Many brain diseases are associated with an alteration in blood-brain barrier (BBB) and its permeability. Current methods using contrast agent are primarily sensitive to major leakage of BBB to macromolecules, but may not detect subtle changes in BBB permeability. The present study aims to develop a novel non-contrast MRI technique for the assessment of BBB permeability to water. Methods The central principle is that by measuring arterially labeled blood spins that are drained into cerebral veins, water extraction fraction ( E ) and permeability-surface-area product ( PS ) of BBB can be determined. Four studies were performed. We first demonstrated the proof-of-principle using conventional ASL with very long post-labeling delays (PLD). Next, a new sequence, dubbed water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST), and its Look-Locker (LL) version were developed. Finally, we demonstrated that the sensitivity of the technique can be significantly enhanced by acquiring the data under mild hypercapnia. Results By combining a strong background suppression with long PLDs (2500–4500 ms), ASL spins were reliably detected in the superior sagittal sinus (SSS), demonstrating the feasibility of measuring this signal. The WEPCAST sequence eliminated partial voluming effects of tissue perfusion and allowed quantitative estimation of E  = 95.5 ± 1.1% and PS  = 188.9 ± 13.4 mL/100 g/min, which were in good agreement with literature reports. LL-WEPCAST sequence shortened the scan time from 19 min to 5 min while providing results consistent with multiple single-PLD acquisitions. Mild hypercapnia increased SNR by 78 ± 25% without causing a discomfort in participants. Conclusion A new non-contrast technique for the assessment of global BBB permeability was developed, which may have important clinical applications.

Description: Purpose 3D time-resolved (4D) phase contrast MRI can be used to study muscle contraction. However, 3D coverage with sufficient spatiotemporal resolution can only be achieved by interleaved acquisitions during many repetitions of the motion task, resulting in long scan times. The aim of this study was to develop a compressed sensing accelerated 4D phase contrast MRI technique for quantification of velocities and strain rate of the muscles in the lower leg during active plantarflexion/dorsiflexion. Methods Nine healthy volunteers were scanned during active dorsiflexion/plantarflexion task. For each volunteer, we acquired a reference scan, as well as 4 different accelerated scans (k-space undersampling factors: 3.14X, 4.09X, 4.89X, and 6.41X) obtained using Cartesian Poisson disk undersampling schemes. The data was reconstructed using a compressed sensing pipeline. For each scan, velocity and strain rate values were quantified in the gastrocnemius lateralis, gastrocnemius medialis, tibialis anterior, and soleus. Results No significant differences in velocity values were observed as a function acceleration factor in the investigated muscles. The strain rate calculation resulted in one positive (s + ) and one negative (s − ) eigenvalue, whereas the third eigenvalue (s 3 ) was consistently 0 for all the acquisitions. No significant differences were observed for the strain rate eigenvalues as a function of acceleration factor. Conclusions Data undersampling combined with compressed sensing reconstruction allowed obtainment of time-resolved phase contrast acquisitions with 3D coverage and quantitative information comparable to the reference scan. The 3D sensitivity of the method can help in understanding the connection between muscle architecture and muscle function in future studies.