Magnetic Resonance In Medicine Research Articles

Fast quantitative parameter maps without fitting: Integration yields accurate mono-exponential signal decay rates.

To develop a computationally fast and accurate algorithm for mono-exponential signal modelling and validate the new technique in the context of R2* mapping for iron overload assessment. An algorithm is introduced that directly calculates R2* values from a series of images based on integration of the mono-exponential signal decay curve. The algorithm is fast, because fitting is avoided and only arithmetic computations without iterations are applied. Precision and accuracy of the method is determined in comparison to the conventional log-linear (LL), nonlinear least-squares-based Levenberg-Marquardt (NLM), and squared nonlinear Levenberg-Marquardt (SQNLM) methods, which rely on iterative curve fitting. In simulations, the signal integration based method consistently had the same or better accuracy than the LL, NLM, and SQNLM algorithms for R2* values ranging from 50 s-1 to 1200 s-1 . In phantoms and in vivo (12 participants), this method was robust over a wide range of R2* values and signal-to-noise ratios. Computation times were approximately 100, 1460, and 930 times faster than those of the LL, NLM, and SQNLM methods, respectively. The fast signal integration method accurately calculates R2* maps. It has the potential to replace conventional, mono-exponential fitting methods for quantitative MRI such as R2* parameter mapping. Magn Reson Med 79:2978-2985, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Magnetic resonance molecular imaging of metastatic breast cancer by targeting extradomain-B fibronectin in the tumor microenvironment.

Non-invasive early accurate detection of malignant breast cancer is paramount to the clinical management of the life-threatening disease. Here, we aim to test a small peptide targeted MRI contrast agent, ZD2-Gd(HP-DO3A), specific to an oncoprotein, extradomain-B fibronectin (EDB-FN), in the tumor microenvironment for MR molecular imaging of breast cancer. EDB-FN expression in 4T1 and MDA-MB-231 cancers was analyzed with quantitative real-time PCR and western blot. Primary and metastatic triple negative breast cancer mouse models were developed using 4T1 and MDA-MB-231 cells. Contrast-enhanced MRI was carried out to evaluate the use of ZD2-Gd(HP-DO3A) in detecting 4T1 and MDA-MB-231 primary and metastatic tumors. EDB-FN was abundantly expressed in the extracellular matrix (ECM) of both the primary and metastatic TNBC tumors. In T1 -weighted MRI, ZD2-Gd(HP-DO3A) generated superior contrast enhancement in primary TNBC tumors than a nonspecific clinical agent Gd(HP-DO3A), during 30 min after contrast injection. ZD2-Gd(HP-DO3A) also produced a significant increase in contrast-to-noise ratio (CNR) of TNBC metastases, enabling sensitive localization and delineation of metastases that occulted in non-contrast-enhanced or Gd(HP-DO3A)-enhanced MRI. These findings potentiate the use of ZD2-Gd(HP-DO3A) for MR molecular imaging of malignant breast cancers to improve the healthcare of breast cancer patients. Magn Reson Med 79:3135-3143, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Shuffled magnetization‐prepared multicontrast rapid gradient‐echo imaging

To develop a novel acquisition and reconstruction method for magnetization-prepared 3-dimensional multicontrast rapid gradient-echo imaging, using Hankel matrix completion in combination with compressed sensing and parallel imaging. A random k-space shuffling strategy was implemented in simulation and in vivo human experiments at 7 T for 3-dimensional inversion recovery, T2 /diffusion preparation, and magnetization transfer imaging. We combined compressed sensing, based on total variation and spatial-temporal low-rank regularizations, and parallel imaging with pixel-wise Hankel matrix completion, allowing the reconstruction of tens of multicontrast 3-dimensional images from 3- or 6-min scans. The simulation result showed that the proposed method can reconstruct signal-recovery curves in each voxel and was robust for typical in vivo signal-to-noise ratio with 16-times acceleration. In vivo studies achieved 4 to 24 times accelerations for inversion recovery, T2 /diffusion preparation, and magnetization transfer imaging. Furthermore, the contrast was improved by resolving pixel-wise signal-recovery curves after magnetization preparation. The proposed method can improve acquisition efficiencies for magnetization-prepared MRI and tens of multicontrast 3-dimensional images could be recovered from a single scan. Furthermore, it was robust against noise, applicable for recovering multi-exponential signals, and did not require any previous knowledge of model parameters. Magn Reson Med 79:62-70, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Simultaneous QSM and metabolic imaging of the brain using SPICE.

To map brain metabolites and tissue magnetic susceptibility simultaneously using a single three-dimensional 1 H-MRSI acquisition without water suppression. The proposed technique builds on a subspace imaging method called spectroscopic imaging by exploiting spatiospectral correlation (SPICE), which enables ultrashort echo time (TE)/short pulse repetition time (TR) acquisitions for 1 H-MRSI without water suppression. This data acquisition scheme simultaneously captures both the spectral information of brain metabolites and the phase information of the water signals that is directly related to tissue magnetic susceptibility variations. In extending this scheme for simultaneous QSM and metabolic imaging, we increase k-space coverage by using dual density sparse sampling and ramp sampling to achieve spatial resolution often required by QSM, while maintaining a reasonable signal-to-noise ratio (SNR) for the spatiospectral data used for metabolite mapping. In data processing, we obtain high-quality QSM from the unsuppressed water signals by taking advantage of the larger number of echoes acquired and any available anatomical priors; metabolite spatiospectral distributions are reconstructed using a union-of-subspaces model. In vivo experimental results demonstrate that the proposed method can produce susceptibility maps at a resolution higher than 1.8 × 1.8 × 2.4 mm3 along with metabolite spatiospectral distributions at a nominal spatial resolution of 2.4 × 2.4 × 2.4 mm3 from a single 7-min MRSI scan. The estimated susceptibility values are consistent with those obtained using the conventional QSM method with 3D multi-echo gradient echo acquisitions. This article reports a new capability for simultaneous susceptibility mapping and metabolic imaging of the brain from a single 1 H-MRSI scan, which has potential for a wide range of applications. Magn Reson Med 79:13-21, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Human umbilical cord blood relaxation times and susceptibility at 3 T.

To characterize the magnetic susceptibility and relaxation times (T1 and T2 ) of fetal blood at 3 T as a function of the hematocrit (Hct) and oxygen saturation (sO2 ). Susceptibility and relaxometry measurements were performed on cord blood specimens (N = 90, derived from six caesarean deliveries) with a range of hematocrits and oxygen saturations (0.09 < Hct < 0.82, 7 < sO2 < 100%). To obtain simple, analytic relationships between MRI properties and blood properties, data were fit to established two-compartment (plasma and erythrocytes) models. Two-compartment models effectively described the cord blood data. The root-mean-squared deviation between the model and the data was 6.3, 10.3, and 1.3% for fits to T1 , T2 , and susceptibility measurements. Relaxometry data and estimated T1 and T2 model parameters were generally consistent with those reported in cord blood at 1.5 T and comparable to published values for adult blood. Notably, the measured value of Δχdeo , the susceptibility difference between fully oxygenated (sO2 = 100%) and deoxygenated (sO2 = 0) cord blood was approximately 20% lower than the established adult blood value (Δχdeo,cord = 2.64 ppm, Δχdeo,adult = 3.4 ppm). The described models and associated parameter values can be used to inform acquisition parameters, and interpret fetal/neonatal blood susceptibility measurements and relaxometry data acquired at 3 T with respect to hematocrit and sO2 . Magn Reson Med 79:3194-3206, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

T1 mapping with the variable flip angle technique: A simple correction for insufficient spoiling of transverse magnetization.

The variable flip angle method derives T1 maps from radiofrequency-spoiled gradient-echo data sets, acquired with different flip angles α. Because the method assumes validity of the Ernst equation, insufficient spoiling of transverse magnetization yields errors in T1 estimation, depending on the chosen radiofrequency-spoiling phase increment (Δϕ). This paper presents a versatile correction method that uses modified flip angles α' to restore the validity of the Ernst equation. Spoiled gradient-echo signals were simulated for three commonly used phase increments Δϕ (50°/117°/150°), different values of α, repetition time (TR), T1 , and a T2 of 85 ms. For each parameter combination, α' (for which the Ernst equation yielded the same signal) and a correction factor CΔϕ (α, TR, T1 ) = α'/α were determined. CΔϕ was found to be independent of T1 and fitted as polynomial CΔϕ (α, TR), allowing to calculate α' for any protocol using this Δϕ. The accuracy of the correction method for T2 values deviating from 85 ms was also determined. The method was tested in vitro and in vivo for variable flip angle scans with different acquisition parameters. The technique considerably improved the accuracy of variable flip angle-based T1 maps in vitro and in vivo. The proposed method allows for a simple correction of insufficient spoiling in gradient-echo data. The required polynomial parameters are supplied for three common Δϕ. Magn Reson Med 79:3082-3092, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Apparent diffusion coefficients of the five major metabolites measured in the human brain in vivo at 3T.

To measure the apparent diffusion coefficients (ADC) of five main metabolites in the human brain at 3T with PRESS and STEAM, avoiding measurement biases because of cross-terms. Cross-terms arise from interactions between slice-selection and spoiler gradients in the localized spectroscopy sequence and the diffusion gradients. Diffusion-weighted spectra were acquired from the prefrontal cortex in five healthy subjects using STEAM (echo time [TE]/mixing time [TM]/pulse repetition time [TR] = 21.22/105/3000 ms, b-values = 0 and 3172 s/mm2 ) and PRESS (TE/TR = 54.2/3000 ms, b-values = 0 and 2204 s/mm2 ). Diffusion weighting was applied using bipolar gradients in three orthogonal directions. Post-processed spectra were analyzed with LCModel, and the trace/3 ADC values were calculated. Comparable trace/3 ADC values (0.14-0.18 µm2 /ms) were obtained for five main metabolites with both methods. These metabolites were quantified with Cramér-Rao lower bounds below 15%. The ADC values of the five main metabolites were successfully measured in the human brain at 3T with eliminated directional dependence. Both STEAM and PRESS can be used to probe the diffusivity of metabolites in normal brain and various pathologies on the clinical scanner with slightly higher precision achieved with STEAM for glutamate and myo-inositol. Magn Reson Med 79:2896-2901, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Development of a quantitative intracranial vascular features extraction tool on 3D MRA using semiautomated open-curve active contour vessel tracing.

To develop a quantitative intracranial artery measurement technique to extract comprehensive artery features from time-of-flight MR angiography (MRA). By semiautomatically tracing arteries based on an open-curve active contour model in a graphical user interface, 12 basic morphometric features and 16 basic intensity features for each artery were identified. Arteries were then classified as one of 24 types using prediction from a probability model. Based on the anatomical structures, features were integrated within 34 vascular groups for regional features of vascular trees. Eight 3D MRA acquisitions with intracranial atherosclerosis were assessed to validate this technique. Arterial tracings were validated by an experienced neuroradiologist who checked agreement at bifurcation and stenosis locations. This technique achieved 94% sensitivity and 85% positive predictive values (PPV) for bifurcations, and 85% sensitivity and PPV for stenosis. Up to 1,456 features, such as length, volume, and averaged signal intensity for each artery, as well as vascular group in each of the MRA images, could be extracted to comprehensively reflect characteristics, distribution, and connectivity of arteries. Length for the M1 segment of the middle cerebral artery extracted by this technique was compared with reviewer-measured results, and the intraclass correlation coefficient was 0.97. A semiautomated quantitative method to trace, label, and measure intracranial arteries from 3D-MRA was developed and validated. This technique can be used to facilitate quantitative intracranial vascular research, such as studying cerebrovascular adaptation to aging and disease conditions. Magn Reson Med 79:3229-3238, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Body diffusion-weighted imaging using magnetization prepared single-shot fast spin echo and extended parallel imaging signal averaging.

This work demonstrates a magnetization prepared diffusion-weighted single-shot fast spin echo (SS-FSE) pulse sequence for the application of body imaging to improve robustness to geometric distortion. This work also proposes a scan averaging technique that is superior to magnitude averaging and is not subject to artifacts due to object phase. This single-shot sequence is robust against violation of the Carr-Purcell-Meiboom-Gill (CPMG) condition. This is achieved by dephasing the signal after diffusion weighting and tipping the MG component of the signal onto the longitudinal axis while the non-MG component is spoiled. The MG signal component is then excited and captured using a traditional SS-FSE sequence, although the echo needs to be recalled prior to each echo. Extended Parallel Imaging (ExtPI) averaging is used where coil sensitivities from the multiple acquisitions are concatenated into one large parallel imaging (PI) problem. The size of the PI problem is reduced by SVD-based coil compression which also provides background noise suppression. This sequence and reconstruction are evaluated in simulation, phantom scans, and in vivo abdominal clinical cases. Simulations show that the sequence generates a stable signal throughout the echo train which leads to good image quality. This sequence is inherently low-SNR, but much of the SNR can be regained through scan averaging and the proposed ExtPI reconstruction. In vivo results show that the proposed method is able to provide diffusion encoded images while mitigating geometric distortion artifacts compared to EPI. This work presents a diffusion-prepared SS-FSE sequence that is robust against the violation of the CPMG condition while providing diffusion contrast in clinical cases. Magn Reson Med 79:3032-3044, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

3D diffusion-weighted 129 Xe MRI for whole lung morphometry.

PurposeTo obtain whole lung morphometry measurements from 129Xe in a single breath‐hold with 3D multiple b‐value 129Xe diffusion‐weighted MRI (DW‐MRI) with an empirically optimized diffusion time and compressed sensing for scan acceleration.MethodsProspective three‐fold undersampled 3D multiple b‐value hyperpolarized 129Xe DW‐MRI datasets were acquired, and the diffusion time (Δ) was iterated so as to provide diffusive length scale (LmD) estimates from the stretched exponential model (SEM) that are comparable to those from 3He. The empirically optimized 129Xe diffusion time was then implemented with a four‐fold undersampling scheme and was prospectively benchmarked against 3He measurements in a cohort of five healthy volunteers, six ex‐smokers, and two chronic obstructive pulmonary disease patients using both SEM‐derived LmD and cylinder model (CM)‐derived mean chord length (Lm).ResultsGood agreement between the mean 129Xe and 3He LmD (mean difference, 2.2%) and Lm (mean difference, 1.1%) values was obtained in all subjects at an empirically optimized 129Xe Δ = 8.5 ms.ConclusionCompressed sensing has facilitated single‐breath 3D multiple b‐value 129Xe DW‐MRI acquisitions, and results at 129Xe Δ = 8.5 ms indicate that 129Xe provides a viable alternative to 3He for whole lung morphometry mapping with either the SEM or CM. Magn Reson Med 79:2986–2995, 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.

Computationally Efficient Combination of Multi-channel Phase Data From Multi-echo Acquisitions (ASPIRE).

To develop a simple method for combining multi-echo phase information from a number of coils in an array that requires no volume coil or additional scans and yields signal-to-noise ratio-optimal images that reflect only ΔB0-related phase. Two SNR optimal coil combination methods were developed which retrieve the ΔB0-related phase by determining the coil-dependent phase offsets. The first variant, MCPC-3D-S, requires the unwrapping of one phase image; the second variant, ASPIRE, allows unwrapping to be avoided if two echoes j and k satisfy the echo time relation m⋅TEk=(m+1)⋅TEj, where m is an integer, making this a particularly fast and robust approach. Both developed methods constitute improvements over a prior method, MCPC-3D, in terms of robustness and computational expense. In the brain at 7 T, phase matching and contrast-to-noise ratio were higher with MCPC-3D-S and ASPIRE than with phase difference reconstruction, and similar to the reference coil-dependent Roemer combination. Unlike the Roemer and virtual reference coil methods, the proposed approaches also eliminated all non- ΔB0-related phase. MCPC-3D-S is an improvement over prior multi-echo methods, which is useful if the ASPIRE echo time condition cannot be fulfilled. ASPIRE is a particularly fast and robust approach that runs on the scanner's reconstructor in a small fraction of the acquisition time. Magn Reson Med 79:2996-3006, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Ghost reduction in echo-planar imaging by joint reconstruction of images and line-to-line delays and phase errors.

To correct line-to-line delays and phase errors in echo-planar imaging (EPI). EPI-trajectory auto-corrected image reconstruction (EPI-TrACR) is an iterative maximum-likelihood technique that exploits data redundancy provided by multiple receive coils between nearby lines of k-space to determine and correct line-to-line trajectory delays and phase errors that cause ghosting artifacts. EPI-TrACR was efficiently implemented using a segmented FFT and was applied to in vivo brain data acquired at 7 T across acceleration (1×-4×) and multishot factors (1-4 shots), and in a time series. EPI-TrACR reduced ghosting across all acceleration factors and multishot factors, compared to conventional calibrated reconstructions and the PAGE method. It also achieved consistently lower ghosting in the time series. Averaged over all cases, EPI-TrACR reduced root-mean-square ghosted signal outside the brain by 27% compared to calibrated reconstruction, and by 40% compared to PAGE. EPI-TrACR automatically corrects line-to-line delays and phase errors in multishot, accelerated, and dynamic EPI. While the method benefits from additional calibration data for initialization, it was not a requirement for most reconstructions. Magn Reson Med 79:3114-3121, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

In vivo characterization of the downfield part of 1 H MR spectra of human brain at 9.4 T: Magnetization exchange with water and relation to conventionally determined metabolite content.

To perform exchange-rate measurements on the in vivo human brain downfield spectrum (5-10 ppm) at 9.4 T and to compare the variation in concentrations of the downfield resonances and of known upfield metabolites to determine potential peak labels. Non-water-suppressed metabolite cycling was used in combination with an inversion transfer technique in two brain locations in healthy volunteers to measure the exchange rates and T1 values of exchanging peaks. Spectra were fitted with a heuristic model of a series of 13 or 14 Voigt lines, and a Bloch-McConnell model was used to fit the exchange rate curves. Concentrations from non-water-inverted spectra upfield and downfield were compared. Mean T1 values ranged from 0.40 to 0.77 s, and exchange rates from 0.74 to 13.8 s-1 . There were no significant correlations between downfield and upfield concentrations, except for N-acetylaspartate, with a correlation coefficient of 0.63 and P < 0.01. Using ultrahigh field allowed improved separation of peaks in the 8.2 to 8.5 ppm amide proton region, and the exchange rates of multiple downfield resonances including the 5.8-ppm peak, previously tentatively assigned to urea, were measured in vivo in human brain. Downfield peaks consisted of overlapping components, and largely missing correlations between upfield and downfield resonances-although not conclusive-indicate limited contributions from metabolites present upfield to the downfield spectrum. Magn Reson Med 79:2863-2873, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Measurement of Murine Single-Kidney Glomerular Filtration Rate Using Dynamic Contrast-Enhanced MRI.

To develop and validate a method for measuring murine single-kidney glomerular filtration rate (GFR) using dynamic contrast-enhanced MRI (DCE-MRI). This prospective study was approved by the Institutional Animal Care and Use Committee. A fast longitudinal relaxation time (T1 ) measurement method was implemented to capture gadolinium dynamics (1 s/scan), and a modified two-compartment model was developed to quantify GFR as well as renal perfusion using 16.4T MRI in mice 2 weeks after unilateral renal artery stenosis (RAS, n = 6) or sham (n = 8) surgeries. This approach was validated by comparing model-derived GFR and perfusion to those obtained by fluorescein isothiocyanante (FITC)-inulin clearance and arterial spin labeling (ASL), respectively, using the Pearson's and Spearman's rank correlations and Bland-Altman analysis. The compartmental model provided a good fitting to measured gadolinium dynamics in both normal and RAS kidneys. The proposed DCE-MRI method offered assessment of single-kidney GFR and perfusion, comparable to the FITC-inulin clearance (Pearson's correlation coefficient r = 0.95 and Spearman's correlation coefficient ρ = 0.94, P < 0.0001, and mean difference -7.0 ± 11.0 μL/min) and ASL (r = 0.92 and ρ = 0.84, P < 0.0001, and mean difference 4.4 ± 66.1 mL/100 g/min) methods. The proposed DCE-MRI method may be useful for reliable noninvasive measurements of single-kidney GFR and perfusion in mice. Magn Reson Med 79:2935-2943, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Accelerated multicontrast volumetric imaging with isotropic resolution for improved peri-infarct characterization using parallel imaging, low-rank and spatially varying edge-preserving sparse modeling.

To achieve consistent effectiveness in reconstruction of fine image features for cases of varying contrast-to-noise ratio (CNR) to facilitate translating accelerated multicontrast volumetric imaging with isotropic resolution toward clinical utility in peri-infarct characterization. A low-rank and spatially varying edge-preserving constrained compressed sensing parallel imaging reconstruction method (CP-LASER) is developed to effectively preserve contrast of small-scale structures for highly accelerated multicontrast volumetric imaging in CNR-limited scenarios. CP-LASER synergistically integrates parallel imaging, low-rank and spatially varying edge-preserving sparse modeling to achieve high signal-to-noise-ratio efficiency by leveraging prior knowledge about signal properties including coil sensitivity weighting, spatiotemporally correlated signal relaxation, and spatially varying sparsity. In the preclinical study using highly accelerated multicontrast volumetric imaging with an isotropic 1.5-mm resolution, CP-LASER demonstrated robust multicontrast reconstruction of peri-infarct characteristics with excellent correspondence with histopathology. CP-LASER provides better delineation of the peri-infarct border zone with improved sharpness than alternative methods in a clinical demonstration on 1.5T with an isotropic 2.2-mm resolution achieved in a single breath-hold. Accelerated multicontrast volumetric imaging with isotropic resolution using CP-LASER has demonstrated the potential to improve peri-infarct characterization in a clinical setting. Magn Reson Med 79:3018-3031, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Reproducibility of CMRO2 determination using dynamic 17O MRI

To assess the reproducibility of 17 O MRI-based determination of the cerebral metabolic rate of oxygen consumption (CMRO2 ) in healthy volunteers. To assess the influence of image acquisition and reconstruction parameters on dynamic quantification of functional parameters such as CMRO2 . Dynamic 17 O MRI data were simulated and used to investigate influences of temporal resolution (Δt) and partial volume correction (PVC) on the determination of CMRO2 . Three healthy volunteers were examined in two separate examinations. In vivo 17 O MRI measurements were conducted with a nominal spatial resolution of (7.5 mm)3 using a density-adapted radial sequence with golden angle acquisition scheme. In each measurement, 4.0 ± 0.1 L of 70%-enriched 17 O gas were administered using a rebreathing system. Data were corrected with a PVC algorithm, and CMRO2 was determined in gray matter (GM) and white matter (WM) compartments using a three-phase metabolic model (baseline, 17 O inhalation, decay phase). Comparison with the ground truth of simulations revealed improved CMRO2 determination after application of PVC and with Δt ≤ 2:00 min. Evaluation of in vivo data yields to CMRO2,GM = 2.31 ± 0.1 μmol/g/min and to CMRO2,WM = 0.69 ± 0.04 μmol/g/min with coefficients of variation (CoV) of 0.3-5.5% and 4.3-5.0% for intra-volunteer and inter-volunteer data, respectively. This in vivo 17 O inhalation study demonstrated that the proposed experimental setup enables reproducible determination of CMRO2 in healthy volunteers. Magn Reson Med 79:2923-2934, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Direct saturation-corrected chemical exchange saturation transfer MRI of glioma: Simplified decoupling of amide proton transfer and nuclear overhauser effect contrasts.

Chemical exchange saturation transfer (CEST) MRI has shown promise in tissue characterization in diseases like stroke and tumor. However, in vivo CEST imaging such as amide proton transfer (APT) MRI is challenging because of concomitant factors such as direct water saturation, macromolecular magnetization transfer, and nuclear overhauser effect (NOE), which lead to a complex contrast in the commonly used asymmetry analysis (MTRasym). Here, we propose a direct saturation-corrected CEST (DISC-CEST) analysis for simplified decoupling and quantification of in vivo CEST effects. CEST MRI and relaxation measurements were carried out on a classical 2-pool creatine-gel CEST phantom and normal rat brains (N = 6) and a rat model of glioma (N = 8) at 4.7T. The proposed DISC-CEST quantification was carried out and compared with conventional MTRasym and the original three-offset method. We demonstrated that the DISC-CEST contrast in the phantom had much stronger correlation with MTRasym than the three-offset method, which showed substantial underestimation. In normal rat brains, the DISC-CEST approach revealed significantly stronger APT effect in gray matter and higher NOE effect in white matter. Furthermore, the APT and NOE maps derived from DISC-CEST showed significantly higher APT effect in the tumors than contralateral normal tissue but no apparent difference in NOE. The proposed DISC-CEST method, by correction of nonlinear direct water saturation effect, serves as a promising alternative to both the commonly used MTRasym and the simplistic three-offset analyses. It provides simple yet reliable in vivo CEST quantification such as APT and NOE mapping in brain tumor, which is promising for clinical translation. Magn Reson Med 78:2307-2314, 2017. © 2017 International Society for Magnetic Resonance in Medicine.

Calculating potential error in sodium MRI with respect to the analysis of small objects.

To facilitate correct interpretation of sodium MRI measurements, calculation of error with respect to rapid signal decay is introduced and combined with that of spatially correlated noise to assess volume-of-interest (VOI) 23 Na signal measurement inaccuracies, particularly for small objects. Noise and signal decay-related error calculations were verified using twisted projection imaging and a specially designed phantom with different sized spheres of constant elevated sodium concentration. As a demonstration, lesion signal measurement variation (5 multiple sclerosis participants) was compared with that predicted from calculation. Both theory and phantom experiment showed that VOI signal measurement in a large 10-mL, 314-voxel sphere was 20% less than expected on account of point-spread-function smearing when the VOI was drawn to include the full sphere. Volume-of-interest contraction reduced this error but increased noise-related error. Errors were even greater for smaller spheres (40-60% less than expected for a 0.35-mL, 11-voxel sphere). Image-intensity VOI measurements varied and increased with multiple sclerosis lesion size in a manner similar to that predicted from theory. Correlation suggests large underestimation of 23 Na signal in small lesions. Acquisition-specific measurement error calculation aids 23 Na MRI data analysis and highlights the limitations of current low-resolution methodologies. Magn Reson Med 79:2968-2977, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Motion robust high resolution 3D free-breathing pulmonary MRI using dynamic 3D image self-navigator.

To achieve motion robust high resolution 3D free-breathing pulmonary MRI utilizing a novel dynamic 3D image navigator derived directly from imaging data. Five-minute free-breathing scans were acquired with a 3D ultrashort echo time (UTE) sequence with 1.25 mm isotropic resolution. From this data, dynamic 3D self-navigating images were reconstructed under locally low rank (LLR) constraints and used for motion compensation with one of two methods: a soft-gating technique to penalize the respiratory motion induced data inconsistency, and a respiratory motion-resolved technique to provide images of all respiratory motion states. Respiratory motion estimation derived from the proposed dynamic 3D self-navigator of 7.5 mm isotropic reconstruction resolution and a temporal resolution of 300 ms was successful for estimating complex respiratory motion patterns. This estimation improved image quality compared to respiratory belt and DC-based navigators. Respiratory motion compensation with soft-gating and respiratory motion-resolved techniques provided good image quality from highly undersampled data in volunteers and clinical patients. An optimized 3D UTE sequence combined with the proposed reconstruction methods can provide high-resolution motion robust pulmonary MRI. Feasibility was shown in patients who had irregular breathing patterns in which our approach could depict clinically relevant pulmonary pathologies. Magn Reson Med 79:2954-2967, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

A comparison of exogenous and endogenous CEST MRI methods for evaluating in vivo pH.

Extracellular pH (pHe) is an important biomarker for cancer cell metabolism. Acido-chemical exchange saturation transfer (CEST) MRI uses the contrast agent iopamidol to create spatial maps of pHe. Measurements of amide proton transfer exchange rates (kex ) from endogenous CEST MRI were compared to pHe measurements by exogenous acido-CEST MRI to determine whether endogenous kex could be used as a proxy for pHe measurements. Spatial maps of pHe and kex were obtained using exogenous acidoCEST MRI and an endogenous CEST MRI analyzed with the omega plot method, respectively, to evaluate mouse kidney, a flank tumor model, and a spontaneous lung tumor model. The pHe and kex results were evaluated using pixelwise comparisons. The kex values obtained from endogenous CEST measurements did not correlate with the pHe results from exogenous CEST measurements. The kex measurements were limited to fewer pixels and had a limited dynamic range relative to pHe measurements. Measurements of kex with endogenous CEST MRI cannot substitute for pHe measurements with acidoCEST MRI. Whereas endogenous CEST MRI may still have good utility for evaluating some specific pathologies, exogenous acido-CEST MRI is more appropriate when evaluating pathologies based on pHe values. Magn Reson Med 79:2766-2772, 2018. © 2017 International Society for Magnetic Resonance in Medicine.