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PURPOSE: To introduce proton density water-fraction (PDWF) as a confounder-corrected MR-based biomarker of mammographic breast density, a known risk factor for breast cancer. METHODS: Chemical shift encoded (CSE) MR images were acquired using a low flip angle to provide proton density contrast from multiple echo times. Fat and water images, corrected for known biases, were produced by a six-echo confounder-corrected (CC) CSE-MRI algorithm. Fibroglandular tissue (FGT) volume was calculated from whole-breast segmented PDWF maps at 1.5T and 3T. The method was evaluated in (1) a physical fat-water phantom and (2) normal volunteers. Results from two- and three-echo CSE-MRI methods were included for comparison. RESULTS: Six-echo CC-CSE-MRI produced unbiased estimates of the total water volume in the phantom (mean bias 3.3%) and was reproducible across protocol changes (repeatability coefficient=14.8 cm(3) and 13.97 cm(3) at 1.5T and 3.0T respectively) and field strengths (repeatability coefficient=51.7 cm(3)) in volunteers, while the two- and three-echo CSE-MRI approaches produced biased results in phantoms (mean bias 30.7% and 10.4%) that was less reproducible across field strengths in volunteers (repeatability coefficient=82.3 cm(3) and 126.3 cm(3)). Significant differences in measured FGT volume was found between the six-echo CC-CSE-MRI and the two- and three-echo CSE-MRI approaches (P = 0.002 and P =0.001). CONCLUSION: The use of six-echo CC-CSE-MRI to create unbiased PDWF maps that reproducibly quantify FGT in the breast is demonstrated. Further studies are needed to correlate this quantitative MR biomarker for breast density with mammography and overall risk for breast cancer.

PURPOSE To evaluate the precision profile (repeatability and reproducibility) of quantitative STEAM-MRS and to determine the relationships between multiple MR biomarkers of chronic liver disease in subjects with iron overload at both 1.5 Tesla (T) and 3T. METHODS MRS data were acquired in patients with known or suspected liver iron overload. Two STEAM-MRS sequences (multi-TE and multi-TE-TR) were acquired at both 1.5T and 3T (same day), including test-retest acquisition. Each acquisition enabled estimation of R1, R2, and FWHM (each separately for water and fat); and proton density fat fraction. The test-retest repeatability and reproducibility across acquisition modes (multi-TE vs. multi-TE-TR) of the estimates were evaluated using intraclass correlation coefficients, linear regression, and Bland-Altman analyses. Multi-parametric relationships between parameters at each field strength, across field strengths, and with liver iron concentration were also evaluated using linear and nonlinear regression. RESULTS Fifty-six (n = 56) subjects (10 to 73 years, 37 males/19 females) were successfully recruited. Both STEAM-MRS sequences demonstrated good-to-excellent precision (intraclass correlation coefficient ≥ 0.81) for the quantification of R1water , R2water , FWHMwater , and proton density fat fraction at both 1.5T and 3T. Additionally, several moderate (R2 = 0.50 to 0.69) to high (R2 ≥ 0.70) correlations were observed between biomarkers, across field strengths, and with liver iron concentration. CONCLUSIONS Over a broad range of liver iron concentration, STEAM-MRS enables rapid and precise measurement of multiple biomarkers of chronic liver disease. By evaluating the multi-parametric relationships between biomarkers, this work may advance the comprehensive MRS-based assessment of chronic liver disease and may help establish biomarkers of chronic liver disease.

Purpose Chemical shift-encoded MRI (CSE-MRI) is well-established to quantify proton density fat fraction (PDFF) as a quantitative biomarker of hepatic steatosis. However, temperature is known to bias PDFF estimation in phantom studies. In this study, strategies were developed and evaluated to correct for the effects of temperature on PDFF estimation through simulations, temperature-controlled experiments, and a multi-center, multi-vendor phantom study. Theory and methods A technical solution that assumes and automatically estimates a uniform, global temperature throughout the phantom is proposed. Computer simulations modeled the effect of temperature on PDFF estimation using magnitude-, complex-, and hybrid-based CSE-MRI methods. Phantom experiments were performed to assess the temperature correction on PDFF estimation at controlled phantom temperatures. To assess the temperature correction method on a larger scale, the proposed method was applied to data acquired as part of a nine-site multi-vendor phantom study and compared to temperature-corrected PDFF estimation using an a priori guess for ambient room temperature. Results Simulations and temperature-controlled experiments show that as temperature deviates further from the assumed temperature, PDFF bias increases. Using the proposed correction method and a reasonable a priori guess for ambient temperature, PDFF bias and variability were reduced using magnitude-based CSE-MRI, across MRI systems, field strengths, protocols, and varying phantom temperature. Complex and hybrid methods showed little PDFF bias and variability both before and after correction. Conclusion Correction for temperature reduces temperature-related PDFF bias and variability in phantoms across MRI vendors, sites, field strengths, and protocols for magnitude-based CSE-MRI, even without a priori information about the temperature.

Purpose The purpose of this work is to characterize the magnitude and variability of B0 and B1 inhomogeneities in the liver in large cohorts of patients at both 1.5 T and 3.0 T. Methods Volumetric B0 and B1 maps were acquired over the liver of patients presenting for routine abdominal MRI. Regions of interest were drawn in the nine Couinaud segments of the liver, and the average value was recorded. Magnitude and variation of measured averages in each segment were reported across all patients. Results A total of 316 B0 maps and 314 B1 maps, acquired at 1.5 T and 3.0 T on a variety of GE Healthcare MRI systems in 630 unique exams, were identified, analyzed, and, in the interest of reproducible research, de-identified and made public. Measured B0 inhomogeneities ranged (5th-95th percentiles) from -31.7 Hz to 164.0 Hz for 3.0 T (-14.5 Hz to 81.3 Hz at 1.5 T), while measured B1 inhomogeneities (ratio of actual over prescribed flip angle) ranged from 0.59 to 1.13 for 3.0 T (0.83 to 1.11 at 1.5 T). Conclusion This study provides robust characterization of B0 and B1 inhomogeneities in the liver to guide the development of imaging applications and protocols. Field strength, bore diameter, and sex were determined to be statistically significant effects for both B0 and B1 uniformity. Typical clinical liver imaging at 3.0 T should expect B0 inhomogeneities ranging from approximately -100 Hz to 250 Hz (-50 Hz to 150 Hz at 1.5 T) and B1 inhomogeneities ranging from approximately 0.4 to 1.3 (0.7 to 1.2 at 1.5 T).

Purpose To propose a motion-robust chemical shift-encoded (CSE) method with high signal-to-noise (SNR) for accurate quantification of liver proton density fat fraction (PDFF) and R 2 ∗ . Methods A free-breathing multi-repetition 2D CSE acquisition with motion-corrected averaging using nonlocal means (NLM) was proposed. PDFF and R 2 ∗ quantified with 2D CSE-NLM were compared to two alternative 2D techniques: direct averaging and single acquisition (2D 1ave) in a digital phantom. Further, 2D NLM was compared in patients to 3D techniques (standard breath-hold, free-breathing and navigated), and the alternative 2D techniques. A reader study and quantitative analysis (Bland-Altman, correlation analysis, paired Student's t-test) were performed to evaluate the image quality and assess PDFF and R 2 ∗ measurements in regions of interest. Results In simulations, 2D NLM resulted in lower standard deviations (STDs) of PDFF (2.7%) and R 2 ∗ (8.2 s - 1 ) compared to direct averaging (PDFF: 3.1%, R 2 ∗ : 13.6 s - 1 ) and 2D 1ave (PDFF: 8.7%, R 2 ∗ : 33.2 s - 1 ). In patients, 2D NLM resulted in fewer motion artifacts than 3D free-breathing and 3D navigated, less signal loss than 2D direct averaging, and higher SNR than 2D 1ave. Quantitatively, the STDs of PDFF and R 2 ∗ of 2D NLM were comparable to those of 2D direct averaging (p>0.05). 2D NLM reduced bias, particularly in R 2 ∗ (-5.73 to -0.36 s - 1 ) that arises in direct averaging (-3.96 to 11.22 s - 1 ) in the presence of motion. Conclusions 2D CSE-NLM enables accurate mapping of PDFF and R 2 ∗ in the liver during free-breathing.

PURPOSE: T1- and T2-weighted (T1w, and T2w) imaging are essential sequences in routine clinical practice to detect and characterize a wide variety of pathologies. Many approaches have been proposed to obtain T1w and T2w contrast although many challenges still remain, including long acquisition time, and limitations that favor 2D imaging, etc. In this study, we propose a novel method for simultaneous T1w and T2w imaging using RF phase-modulated 3D gradient echo (GRE) imaging. THEORY: Configuration theory is used to derive closed form equations for the steady-state of RF phase-modulated GRE signal. These equations suggest the use of small RF phase increments to provide orthogonal signal contrast with T2w and T1w in the real and imaginary components, respectively. Background phase can be removed using a two-pass acquisition with opposite RF phase increments. METHODS: Simulation and phantom experiments were performed to validate our proposed method. Volunteer images of the brain and knee were acquired to demonstrate the clinical feasibility. The proposed method was compared with T1w and T2w fast spin-echo (FSE) imaging. RESULTS: The relative signal intensity of images acquired using the proposed method agreed closely with simulations and FSE imaging in phantoms. Images from volunteer imaging showed very similar contrast compared to conventional FSE imaging. CONCLUSION: RF phase-modulated GRE with small RF phase increments is an alternative method that provides simultaneous T1w and T2w contrast in short scan times with 3D volumetric coverage.

PURPOSE: Transverse relaxation time (T(2)) mapping with MRI has a plethora of clinical and research applications. Current T(2) mapping techniques are based primarily on spin-echo (SE) relaxometry strategies that rely on the signal magnitude, and often suffer from lengthy acquisition times. In this work we propose a phase-based T(2) mapping technique where T(2) information is encoded into the signal phase of rapid gradient echo (GRE) acquisitions. THEORY: Bloch equation simulations demonstrate that the phase of GRE acquisitions obtained with a very small inter-repetition RF phase increment has a strong monotonic dependence on T(2), resulting from coherent transverse magnetization. This T(2)-dependent phase behavior forms the basis of the proposed T(2) mapping technique. To isolate T(2)-dependent phase from background phase, at least two datasets with different RF phase increments are acquired. The proposed method can also be combined with chemical shift encoded MRI to separate water and fat signals. METHODS: The feasibility of the proposed technique was validated in a phantom experiment. In vivo feasibility was demonstrated in the brain, knee, abdomen and pelvis. Comparisons were made with SE-based T(2) mapping, spectroscopy and T(2) values from the literature. RESULTS: The proposed method produced accurate T(2) maps compared with SE-based T(2) mapping in the phantom. Good qualitative agreement was observed in vivo between the proposed method and the reference. T(2) measured in various anatomies agreed well with values reported in the literature. CONCLUSION: A phase-based T(2) mapping technique was developed and its feasibility demonstrated in phantoms and in vivo.

PURPOSE To develop and validate a T1 -corrected chemical-shift encoded MRI (CSE-MRI) method to improve noise performance and reduce bias for quantification of tissue proton density fat-fraction (PDFF). METHODS A variable flip angle (VFA)-CSE-MRI method using joint-fit reconstruction was developed and implemented. In computer simulations and phantom experiments, sources of bias measured using VFA-CSE-MRI were investigated. The effect of tissue T1 on bias using low flip angle (LFA)-CSE-MRI was also evaluated. The noise performance of VFA-CSE-MRI was compared to LFA-CSE-MRI for liver fat quantification. Finally, a prospective pilot study in patients undergoing gadoxetic acid-enhanced MRI of the liver to evaluate the ability of the proposed method to quantify liver PDFF before and after contrast. RESULTS VFA-CSE-MRI was accurate and insensitive to transmit B1 inhomogeneities in phantom experiments and computer simulations. With high flip angles, phase errors because of RF spoiling required modification of the CSE signal model. For relaxation parameters commonly observed in liver, the joint-fit reconstruction improved the noise performance marginally, compared to LFA-CSE-MRI, but eliminated T1 -related bias. A total of 25 patients were successfully recruited and analyzed for the pilot study. Strong correlation and good agreement between PDFF measured with VFA-CSE-MRI and LFA-CSE-MRI (pre-contrast) was observed before (R2 = 0.97; slope = 0.88, 0.81-0.94 95% confidence interval [CI]; intercept = 1.34, -0.77-1.92 95% CI) and after (R2 = 0.93; slope = 0.88, 0.78-0.98 95% CI; intercept = 1.90, 1.01-2.79 95% CI) contrast. CONCLUSION Joint-fit VFA-CSE-MRI is feasible for T1 -corrected PDFF quantification in liver, is insensitive to B1 inhomogeneities, and can eliminate T1 bias, but with only marginal SNR advantage for T1 values observed in the liver.

PURPOSE: The purpose of this work is to characterize the magnitude and variability of B0 and B1 inhomogeneities in the liver in large cohorts of patients at both 1.5T and 3.0T. METHODS: Volumetric B0 and B1 maps were acquired over the liver of patients presenting for routine abdominal MRI. Regions of interest were drawn in the nine Couinaud segments of the liver and the average value was recorded. Magnitude and variation of measured averages in each segment were reported across all patients. RESULTS: A total of 316 B0 maps and 314 B1 maps, acquired at 1.5T and 3.0T on a variety of GE Healthcare MRI systems in 630 unique exams, were identified, analyzed, and, in the interest of reproducible research, de-identified and made public. Measured B0 inhomogeneities ranged (5th-95th percentiles) from −31.7Hz to 164.0Hz for 3.0T (−14.5Hz to 81.3Hz at 1.5T), while measured B1 inhomogeneities (ratio of actual over prescribed flip angle) ranged from 0.59 to 1.13 for 3.0T (0.83 to 1.11 at 1.5T). CONCLUSION: This study provides robust characterization of B0 and B1 inhomogeneities in the liver to guide the development of imaging applications and protocols. Field strength, bore diameter, and sex were determined to be statistically significant effects for both B0 and B1 uniformity. Typical clinical liver imaging at 3.0T should expect B0 inhomogeneities ranging from approximately −100Hz to 250Hz (−50Hz to 150Hz at 1.5T) and B1 inhomogeneities ranging from approximately 0.4 to 1.3 (0.7 to 1.2 at 1.5T).

PURPOSE: To design, construct, and evaluate quantitative MR phantoms that mimic MRI signals from the liver with simultaneous control of three parameters: proton-density fat-fraction (PDFF), [Formula: see text] , and T(1). These parameters are established biomarkers of hepatic steatosis, iron overload, and fibrosis/inflammation, respectively, which can occur simultaneously in the liver. METHODS: Phantoms including multiple vials were constructed. Peanut oil was used to modulate PDFF, MnCl(2) and iron microspheres were used to modulate [Formula: see text] , and NiCl(2) was used to modulate the T(1) of water (T(1,water)). Phantoms were evaluated at both 1.5T and 3.0T using stimulated echo acquisition mode MR spectroscopy (STEAM-MRS) and chemical shift encoded (CSE) MRI. STEAM-MRS data were processed to estimate T(1,water), T(1,fat), [Formula: see text] , and [Formula: see text] for each vial. CSE-MRI data were processed to generate PDFF and [Formula: see text] maps, and measurements were obtained in each vial. Measurements were evaluated using linear regression and Bland-Altman analysis. RESULTS: High quality PDFF and [Formula: see text] maps were obtained with homogeneous values throughout each vial. High correlation was observed between imaging PDFF with target PDFF (slope=0.94–0.97, R(2)=0.994–0.997) and imaging [Formula: see text] with target [Formula: see text] (slope=0.84–0.88, R(2)=0.935–0.943) at both 1.5T and 3.0T. [Formula: see text] and [Formula: see text] were highly correlated with slope close to 1.0 at both 1.5T (slope=0.90, R(2)=0.988) and 3.0T (slope=0.99, R(2)=0.959), similar to the behavior observed in vivo. T(1,water) (500–1200ms) was controlled with varying NiCl(2) concentration, while T(1,fat) (300ms) was independent of NiCl(2) concentration. CONCLUSION: Novel quantitative MRI phantoms that mimic the simultaneous presence of fat, iron, and fibrosis in the liver were successfully developed and validated. KEYWORDS: Quantitative imaging biomarkers, phantom, proton-density fat-fraction, [Formula: see text] , T(1), liver

Purpose To assess the reproducibility of biexponential R2 -relaxometry MRI for estimation of liver iron concentration (LIC) between proprietary and nonproprietary analysis methods. Methods This single-center retrospective study, approved by investigational review board and compliant with the Health Insurance Portability and Accountability Act, included 40 liver MRI exams in 38 subjects with suspected or known iron overload. From spin-echo images of the liver, acquired at 5 different echo times (TE = 6-18 ms), biexponential R2 maps were calculated using 1 proprietary (FerriScan, Resonance Health Ltd., Claremont WA, Australia) and 3 nonproprietary (simulated annealing, nonlinear least squares, dictionary search) analysis methods. Each subject's average liver R2 value was converted to LIC using a previously validated calibration curve. Inter-method reproducibility for liver R2 and LIC were assessed for linearity using linear regression analysis and absolute agreement using intraclass correlation and Bland-Altman analysis. For point estimates, 95% confidence intervals were calculated; P values Results Linearity between the proprietary and nonproprietary methods was excellent across the observed range for R2 (20-312 s-1 ) and LIC (0.4-52.2 mg/g), with all coefficients of determination (R2 ) ≥ 0.95. No statistically significant bias was found (slope estimates ∼ 1; intercept estimates ∼ 0; P values > 0.05). Agreement between the 4 methods was excellent for both liver R2 and LIC (intraclass correlations ≥ 0.97). Bland-Altman 95% limits of agreement in % difference between the proprietary and nonproprietary methods were ≤ 9% and ≤ 16% for R2 and LIC, respectively. Conclusion Biexponential R2 -relaxometry MRI for LIC estimation is reproducible between proprietary and nonproprietary analysis methods.

Purpose To develop a volumetric imaging technique with 0.8-mm isotropic resolution and 10-s/volume rate to detect and analyze breast lesions in a bilateral, dynamic, contrast-enhanced MRI exam. Methods A local low-rank temporal reconstruction approach that also uses parallel imaging and spatial compressed sensing was designed to create rapid volumetric frame rates during a contrast-enhanced breast exam (vastly undersampled isotropic projection [VIPR] spatial compressed sensing with temporal local low-rank [STELLR]). The dynamic-enhanced data are subtracted in k-space from static mask data to increase sparsity for the local low-rank approach to maximize temporal resolution. A T1 -weighted 3D radial trajectory (VIPR iterative decomposition with echo asymmetry and least squares estimation [IDEAL]) was modified to meet the data acquisition requirements of the STELLR approach. Additionally, the unsubtracted enhanced data are reconstructed using compressed sensing and IDEAL to provide high-resolution fat/water separation. The feasibility of the approach and the dual reconstruction methodology is demonstrated using a 16-channel breast coil and a 3T MR scanner in 6 patients. Results The STELLR temporal performance of subtracted data matched the expected temporal perfusion enhancement pattern in small and large vascular structures. Differential enhancement within heterogeneous lesions is demonstrated with corroboration from a basic reconstruction using a strict 10-second temporal footprint. Rapid acquisition, reliable fat suppression, and high spatiotemporal resolution are presented, despite significant data undersampling. Conclusion The STELLR reconstruction approach of 3D radial sampling with mask subtraction provides a high-performance imaging technique for characterizing enhancing structures within the breast. It is capable of maintaining temporal fidelity, while visualizing breast lesions with high detail over a large FOV to include both breasts.

Purpose The purpose of this work is to characterize the noise distribution of proton density fat fraction (PDFF) measured using chemical shift-encoded MRI, and to provide alternative strategies to reduce bias in PDFF estimation. Theory We derived the probability density function for PDFF estimated using chemical shift-encoded MRI, and found it to exhibit an asymmetric noise distribution that contributes to signal-to-noise-ratio dependent bias. Methods To study PDFF noise bias, we performed (at 1.5 T) numerical simulations, phantom acquisitions, and a retrospective in vivo experiment. In each experiment, we compared the performance of three statistics (mean, median, and maximum likelihood estimator) in estimating the PDFF in a region of interest. Results We demonstrated the presence of the asymmetric noise distribution in simulations, phantoms, and in vivo. In each experiment we demonstrated that both the median and proposed maximum likelihood estimator statistics outperformed the mean statistic in mitigating noise-related bias for low signal-to-noise-ratio acquisitions. Conclusions Characterization of the noise distribution of PDFF estimated using chemical shift-encoded MRI enabled new strategies based on median and maximum likelihood estimator statistics to mitigate noise-related bias for accurate PDFF measurement from a region of interest. Such strategies are important for quantitative chemical shift-encoded MRI applications that typically operate in low signal-to-noise-ratio regimes. Magn Reson Med 80:685-695, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Purpose To propose a simple method to correct vascular input function (VIF) due to inflow effects and to test whether the proposed method can provide more accurate VIFs for improved pharmacokinetic modeling. Methods A spoiled gradient echo sequence-based inflow quantification and contrast agent concentration correction method was proposed. Simulations were conducted to illustrate improvement in the accuracy of VIF estimation and pharmacokinetic fitting. Animal studies with dynamic contrast-enhanced MR scans were conducted before, 1 week after, and 2 weeks after portal vein embolization (PVE) was performed in the left portal circulation of pigs. The proposed method was applied to correct the VIFs for model fitting. Pharmacokinetic parameters fitted using corrected and uncorrected VIFs were compared between different lobes and visits. Results Simulation results demonstrated that the proposed method can improve accuracy of VIF estimation and pharmacokinetic fitting. In animal study results, pharmacokinetic fitting using corrected VIFs demonstrated changes in perfusion consistent with changes expected after PVE, whereas the perfusion estimates derived by uncorrected VIFs showed no significant changes. Conclusion The proposed correction method improves accuracy of VIFs and therefore provides more precise pharmacokinetic fitting. This method may be promising in improving the reliability of perfusion quantification. Magn Reson Med 79:3093-3102, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

PURPOSE Cerebral perfusion is commonly assessed clinically with dynamic susceptibility contrast MRI using a bolus injection of gadolinium-based contrast agents, resulting in semi-quantitative values of cerebral blood volume (CBV). Steady-state imaging with ferumoxytol allows estimation of CBV with the potential for higher precision and accuracy. Prior CBV studies have focused on the signal disrupting T2* effects, but ferumoxytol also has high signal-enhancing T1 relaxivity. The purpose of this study was to investigate and compare CBV estimation using T1 and T2*, with the goal of understanding the contrast mechanisms and quantitative differences. METHODS Changes in R1 (1/T1 ) and R2* (1/ T2*) were measured after the administration of ferumoxytol using high-resolution quantitative approaches. Images were acquired at 3.0T and R1 was estimated from an ultrashort echo time variable flip angle approach, while R2* was estimated from a multiple gradient echo sequence. Twenty healthy volunteers were imaged at two doses. CBV was derived and compared from relaxometry in gray and white matter using different approaches. RESULTS R1 measurements showed a linear dependence of blood R1 with respect to dose in large vessels, in contrast to the nonlinear dose-dependence of blood R2* estimates. In the brain parenchyma, R2* showed linear dose-dependency whereas R1 showed nonlinearity. CBV calculations based on R2* changes in tissue and ferumoxytol blood concentration estimates based on R1 relaxivity showed the lowest variability in our cohort. CONCLUSIONS CBV measurements were successfully derived using a combined approach of R1 and R2* relaxometry. Magn Reson Med 79:3072-3081, 2018. © 2017 International Society for Magnetic Resonance in Medicine.

Purpose The purpose of this work was to characterize the effects of concomitant gradients (CGs) on chemical shift encoded (CSE)-based estimation of B0 field map, proton density fat fraction (PDFF), and R2*. Theory A theoretical framework was used to determine the effects of CG-induced phase errors on CSE-MRI data. Methods Simulations, phantom experiments, and in vivo experiments were conducted at 3 Tesla to assess the effects of CGs on quantitative CSE-MRI techniques. Correction of phase errors attributable to CGs was also investigated to determine whether these effects could be removed. Results Phase errors attributed to CGs introduce errors in the estimation of B0 field map, PDFF, and R2*. Phantom and in vivo experiments demonstrated that CGs can introduce estimation errors greater than 30 Hz in the B0 field map, 10% in PDFF, and 16 s−1 in R2*, 16 cm off isocenter. However, CG phase correction before parameter estimation was able to reduce estimation errors to less than 10 Hz in the B0 field map, 1% in PDFF, and 2 s−1 in R2*. Conclusion CG effects can impact CSE-MRI, leading to inaccurate estimation of B0 field map, PDFF, and R2*. However, correction for phase errors caused by CGs improve the accuracy of quantitative parameters estimated from CSE-MRI acquisitions. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine

Purpose We aimed to determine the agreement between quantitative susceptibility mapping (QSM)-based biomagnetic liver susceptometry (BLS) and confounder-corrected R2* mapping with superconducting quantum interference device (SQUID)-based biomagnetic liver susceptometry in patients with liver iron overload. Methods Data were acquired from two healthy controls and 22 patients undergoing MRI and SQUID-BLS as part of routine monitoring for iron overload. Magnetic resonance imaging was performed on a 3T system using a three-dimensional multi-echo gradient-echo acquisition. Both magnetic susceptibility and R2* of the liver were estimated from this acquisition. Linear regression was used to compare estimates of QSM-BLS and R2* to SQUID-BLS. Results Both QSM-BLS and confounder-corrected R2* were sensitive to the presence of iron in the liver. Linear regression between QSM-BLS and SQUID-BLS demonstrated the following relationship: QSM-BLS = (−0.22 ± 0.11) + (0.49 ± 0.05) · SQUID-BLS with r2 = 0.88. The coefficient of determination between liver R2* and SQUID-BLS was also r2 = 0.88. Conclusion We determined a strong correlation between both QSM-BLS and confounder-corrected R2* to SQUID-BLS. This study demonstrates the feasibility of QSM-BLS and confounder-corrected R2* for assessing liver iron overload, particularly when SQUID systems are not accessible. Magn Reson Med 78:264–270, 2017. © 2016 International Society for Magnetic Resonance in Medicine

PURPOSE To develop an externally calibrated parallel imaging technique for three-dimensional multispectral imaging (3D-MSI) in the presence of metallic implants. THEORY AND METHODS A fast, ultrashort echo time (UTE) calibration acquisition is proposed to enable externally calibrated parallel imaging techniques near metallic implants. The proposed calibration acquisition uses a broadband radiofrequency (RF) pulse to excite the off-resonance induced by the metallic implant, fully phase-encoded imaging to prevent in-plane distortions, and UTE to capture rapidly decaying signal. The performance of the externally calibrated parallel imaging reconstructions was assessed using phantoms and in vivo examples. RESULTS Phantom and in vivo comparisons to self-calibrated parallel imaging acquisitions show that significant reductions in acquisition times can be achieved using externally calibrated parallel imaging with comparable image quality. Acquisition time reductions are particularly large for fully phase-encoded methods such as spectrally resolved fully phase-encoded three-dimensional (3D) fast spin-echo (SR-FPE), in which scan time reductions of up to 8 min were obtained. CONCLUSION A fully phase-encoded acquisition with broadband excitation and UTE enabled externally calibrated parallel imaging for 3D-MSI, eliminating the need for repeated calibration regions at each frequency offset. Significant reductions in acquisition time can be achieved, particularly for fully phase-encoded methods like SR-FPE. Magn Reson Med 77:2303-2309, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Author(s): Hernando, Diego; Sharma, Samir D; Aliyari Ghasabeh, Mounes; Alvis, Bret D; Arora, Sandeep S; Hamilton, Gavin; Pan, Li; Shaffer, Jean M; Sofue, Keitaro; Szeverenyi, Nikolaus M; Welch, E Brian; Yuan, Qing; Bashir, Mustafa R; Kamel, Ihab R; Rice, Mark J; Sirlin, Claude B; Yokoo, Takeshi; Reeder, Scott B | Abstract: PurposeTo evaluate the accuracy and reproducibility of quantitative chemical shift-encoded (CSE) MRI to quantify proton-density fat-fraction (PDFF) in a fat-water phantom across sites, vendors, field strengths, and protocols.MethodsSix sites (Philips, Siemens, and GE Healthcare) participated in this study. A phantom containing multiple vials with various oil/water suspensions (PDFF:0%-100%) was built, shipped to each site, and scanned at 1.5T and 3T using two CSE protocols per field strength. Confounder-corrected PDFF maps were reconstructed using a common algorithm. To assess accuracy, PDFF bias and linear regression with the known PDFF were calculated. To assess reproducibility, measurements were compared across sites, vendors, field strengths, and protocols using analysis of covariance (ANCOVA), Bland-Altman analysis, and the intraclass correlation coefficient (ICC).ResultsPDFF measurements revealed an overall absolute bias (across sites, field strengths, and protocols) of 0.22% (95% confidence interval, 0.07%-0.38%) and R2 g 0.995 relative to the known PDFF at each site, field strength, and protocol, with a slope between 0.96 and 1.02 and an intercept between -0.56% and 1.13%. ANCOVA did not reveal effects of field strength (P = 0.36) or protocol (P = 0.19). There was a significant effect of vendor (F = 25.13, P = 1.07 × 10-10 ) with a bias of -0.37% (Philips) and -1.22% (Siemens) relative to GE Healthcare. The overall ICC was 0.999.ConclusionCSE-based fat quantification is accurate and reproducible across sites, vendors, field strengths, and protocols. Magn Reson Med 77:1516-1524, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Purpose To develop a multiband radiofrequency (RF) excitation strategy for simultaneous excitation of multiple RF offsets to accelerate fully phase-encoded imaging near metallic prostheses. Methods Multiband RF excitation was designed and incorporated into a spectrally resolved fully phase-encoded (SR-FPE) imaging scheme. A triband (−6, 0, 6 kHz) acquisition was compared with three separate single-band acquisitions at the corresponding RF offsets with a phantom containing the head of a hip prosthesis. In vivo multiband data with continuous spectral coverage were acquired in the knee of a healthy volunteer with the head of a hip prosthesis placed posteriorly and in a volunteer with a total knee prosthetic implant. Results Phantom images acquired with triband excitation were essentially identical to the composite of three single-band excitations, but with an acceleration factor of three. In vivo multiband images of the healthy knee with adjacent metal demonstrated very good depiction of knee anatomy. In vivo images of the total knee replacement were successfully acquired, allowing visualization of native tissue with far less signal dropout than 2D-FSE. Conclusions FPE imaging with multiband excitation is feasible in the presence of extreme off-resonance. This approach can reduce scan time and/or increase off-resonance coverage, enabling in vivo FPE imaging near metallic prostheses over a broad off-resonance spectrum. Magn Reson Med 77:1223–1230, 2017. © 2016 International Society for Magnetic Resonance in Medicine

Ferumoxytol is an ultrasmall superparamagnetic iron oxide agent marketed for the treatment of anemia. There has been increasing interest in its properties as an MRI contrast agent as well as greater awareness of its adverse event profile. This mini-review summarizes the current state of knowledge of the risks of ferumoxytol and methods of administration.

Purpose To develop and validate closed form mathematical expressions that predict the optimal contrast agent concentration for the maximum T1-weighted spoiled gradient echo (SGRE) signal. Theory and Methods Gadolinium and iron-based contrast agents can have significant transverse relaxivity that leads to signal dropout with increasing contrast agent concentration. A mathematical expression for the “optimal” contrast agent concentration where recovery of longitudinal magnetization is offset by increasing transverse signal decay was derived. Expressions for the maximum possible SGRE signal were also derived. Three phantoms were constructed, each with varying concentrations of one of the following three agents: gadoteridol, gadobenate dimeglumine, and ferumoxytol. After measuring the longitudinal and transverse relaxivity of the three agents, the SGRE signal was measured in the phantoms over a wide range of flip angles and echo times. Results Excellent qualitative agreement between the SGRE signal behavior, optimal concentration, and optimal flip angle were observed between experimental measurements and theoretical predictions. Conclusion This work provides validated mathematical expressions for contrast enhanced T1-weighted SGRE imaging and may provide guidance for contrast dosing and injection protocols, as well as for novel pulse sequence design. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Purpose To evaluate the impact of different fat spectral models on proton density fat fraction quantification using chemical shift-encoded MRI (CSE-MRI). Methods In a simulation study, spectral models of fat were compared pairwise. Comparison of magnitude fitting and mixed fitting was performed over a range of echo times and fat fractions. In vivo acquisitions from 41 patients were reconstructed using seven published spectral models of fat. T2-corrected stimulated echo acquisition mode MR spectroscopy was used as a reference. Results The simulations demonstrated that imperfectly calibrated spectral models of fat result in biases that depend on echo times and fat fraction. Mixed fitting was more robust against this bias than magnitude fitting. Multipeak spectral models showed much smaller differences among themselves than from the single-peak spectral model. In vivo studies showed that all multipeak models agreed better (for mixed fitting, the slope ranged from 0.967 to 1.045 using linear regression) with the reference standard than the single-peak model (for mixed fitting, slope = 0.76). Conclusion It is essential to use a multipeak fat model for accurate quantification of fat with CSE-MRI. Furthermore, fat quantification techniques using multipeak fat models are comparable, and no specific choice of spectral model has been shown to be superior to the rest. Magn Reson Med, 2015. © 2015 Wiley Periodicals, Inc.

Purpose Demonstration of feasibility and protocol optimization for the combined use of gadofosveset trisodium with gadoxetic acid for delayed T1-weighted liver MRI. Methods Eleven healthy volunteers underwent hepatobiliary phase imaging at 3 Tesla (T) using gadoxetic acid. Multiple breathheld T1-weighted three-dimensional spoiled gradient echo sequences were performed at varying flip angles before and after injection of gadofosveset. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured to determine optimal T1-weighting. Examples of three patients with focal liver lesions were acquired. Results The addition of gadofosveset to the hepatobiliary phase of gadoxetic acid renders vessels isointense to liver tissue at low flip angles due to increased vessel SNR (P

The purpose of this work is to characterize the noise distribution of proton density fat fraction (PDFF) measured using chemical shift-encoded MRI, and to provide alternative strategies to reduce bias in PDFF estimation.We derived the probability density function for PDFF estimated using chemical shift-encoded MRI, and found it to exhibit an asymmetric noise distribution that contributes to signal-to-noise-ratio dependent bias.To study PDFF noise bias, we performed (at 1.5 T) numerical simulations, phantom acquisitions, and a retrospective in vivo experiment. In each experiment, we compared the performance of three statistics (mean, median, and maximum likelihood estimator) in estimating the PDFF in a region of interest.We demonstrated the presence of the asymmetric noise distribution in simulations, phantoms, and in vivo. In each experiment we demonstrated that both the median and proposed maximum likelihood estimator statistics outperformed the mean statistic in mitigating noise-related bias for low signal-to-noise-ratio acquisitions.Characterization of the noise distribution of PDFF estimated using chemical shift-encoded MRI enabled new strategies based on median and maximum likelihood estimator statistics to mitigate noise-related bias for accurate PDFF measurement from a region of interest. Such strategies are important for quantitative chemical shift-encoded MRI applications that typically operate in low signal-to-noise-ratio regimes. Magn Reson Med 80:685-695, 2018. © 2018 International Society for Magnetic Resonance in Medicine.

Purpose To characterize the fundamental limits of MRI near metallic implants on RF excitation, frequency encoding, and chemical shift–encoding water–fat separation. Methods Multicomponent three-dimensional (3D) digital models of a total hip and a total knee replacement were used to construct material-specific susceptibility maps. The fundamental limits and spatial relationship of imaging near metallic prostheses were investigated as a function of distance from the prosthetic surface by calculating 3D field map perturbations using a well-validated k-space based dipole kernel. Results Regions limited by the bandwidth of RF excitation overlap substantially with those fundamentally limited by frequency encoding. Rapid breakdown of water–fat separation occurs once the intravoxel off-resonance exceeds ∼6 ppm over a full range of fat fractions (0%–100%) and SNR (5–100). Conclusion Current 3D multispectral imaging methods would not benefit greatly from exciting spins beyond ±12 kHz despite the presence of signal that lies outside of this range from tissue directly adjacent to the metallic implants. Methods such as phase encoding in all three spatial dimensions are necessary to spatially resolve spins beyond an excitation bandwidth of ±12 kHz. The approach described in this study provides a benchmark for the capabilities of current imaging techniques to guide development of new MRI methods for imaging near metal. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.

Purpose: The purpose of this work was to develop and demonstrate feasibility and initial clinical validation of quantitative susceptibility mapping (QSM) in the abdomen as an imaging biomarker of hepatic iron overload. Theory and Methods: In general, QSM is faced with the challenges of background field removal and dipole inversion. Respiratory motion, the presence of fat, and severe iron overload further complicate QSM in the abdomen. We propose a technique for QSM in the abdomen that addresses these challenges. Data were acquired from 10 subjects without hepatic iron overload and 33 subjects with known or suspected iron overload. The proposed technique was used to estimate the susceptibility map in the abdomen, from which hepatic iron overload was measured. As a reference, spin-echo data were acquired for R2-based LIC estimation. Liver R2* was measured for correlation with liver susceptibility estimates. Results: Correlation between susceptibility and R2-based LIC estimation was R2 = 0.76 at 1.5 Tesla (T) and R2 = 0.83 at 3T. Furthermore, high correlation between liver susceptibility and liver R2* (R2 = 0.94 at 1.5T; R2 = 0.93 at 3T) was observed. Conclusion: We have developed and demonstrated initial validation of QSM in the abdomen as an imaging biomarker of hepatic iron overload. Magn Reson Med 74:673–683, 2015. © 2014 Wiley Periodicals, Inc.

Purpose Two-point fat–water separation methods are increasingly being used for chest and abdominal MRI and have recently been introduced for use in MR angiography of the lower extremities. With these methods, flowing spins can accumulate unintended phase shifts between the echo times. The purpose of this study is to demonstrate that these phase shifts can lead to inaccurate signals in the water and fat images. Theory and Methods In vitro experiments were conducted at 1.5T and 3.0T using a stenosis-mimicking phantom and a computer-controlled pump to image a range of physiologically relevant velocities. Results In the phantom images acquired using bipolar readout gradients, fat–water signal inaccuracies were visible in regions of flow, with increasing severity as the flow rate was increased. Additionally, similar effects were observed in regions of high flow in clinical chest and liver exams. In the phantom images, the effect was eliminated by using a dual-pass method without bipolar readout gradients. Conclusion When using fat–water separation methods with bipolar readout gradients, phase shifts caused by the motion of spins can lead to signal inaccuracies in the fat and water images. These artifacts can be mitigated by using approaches that do not use bipolar readout gradients. Magn Reson Med 73:1926–1931, 2015. © 2014 Wiley Periodicals, Inc.

Purpose To develop and evaluate a method for volumetric contrast-enhanced MR imaging of the liver, with high spatial and temporal resolutions, for combined dynamic imaging and MR angiography using a single injection of contrast.

Purpose The purpose of this work was to improve the robustness of existing chemical shift encoded water–fat separation methods by incorporating object-based information of the B0 field inhomogeneity. Theory The primary challenge in water–fat separation is the estimation of phase shifts that arise from B0 field inhomogeneity, which is composed of the background field and susceptibility-induced field. The susceptibility-induced field can be estimated if the susceptibility distribution is known or can be approximated. In this work, the susceptibility distribution is approximated from the source images using the known susceptibility values of water, fat, and air. The field estimate is then demodulated from the source images before water–fat separation. Methods Chemical shift encoded source images were acquired in anatomical regions that are prone to water–fat swaps. The images were processed using algorithms from the ISMRM Fat-Water Toolbox, with and without the object-based field map information. The estimates were compared to examine the benefit of using the object-based field map information. Results Multiple cases are shown in which water–fat swaps were avoided by using the object-based information of the B0 field map. Conclusion Object-based information of the B0 field may improve the robustness of existing chemical shift encoded water–fat separation methods. Magn Reson Med 73:597–604, 2015. © 2014 Wiley Periodicals, Inc.

Purpose To demonstrate feasibility of exploiting the spatial distribution of off-resonance surrounding metallic implants for accelerating multispectral imaging techniques. Theory and Methods Multispectral imaging (MSI) techniques perform time-consuming independent three-dimensional acquisitions with varying radio frequency offsets to address the extreme off-resonance from metallic implants. Each off-resonance bin provides a unique spatial sensitivity that is analogous to the sensitivity of a receiver coil and, therefore, provides a unique opportunity for acceleration. Fully sampled MSI was performed to demonstrate retrospective acceleration. A uniform sampling pattern across off-resonance bins was compared with several adaptive sampling strategies using a total hip replacement phantom. Monte Carlo simulations were performed to compare noise propagation of two of these strategies. With a total knee replacement phantom, positive and negative off-resonance bins were strategically sampled with respect to the B0 field to minimize aliasing. Reconstructions were performed with a parallel imaging framework to demonstrate retrospective acceleration. Results An adaptive sampling scheme dramatically improved reconstruction quality, which was supported by the noise propagation analysis. Independent acceleration of negative and positive off-resonance bins demonstrated reduced overlapping of aliased signal to improve the reconstruction. Conclusion This work presents the feasibility of acceleration in the presence of metal by exploiting the spatial sensitivities of off-resonance bins. Magn Reson Med 72:1658–1667, 2014. © 2014 Wiley Periodicals, Inc.

Purpose To develop and evaluate a free-breathing chemical-shift-encoded (CSE) spoiled gradient-recalled echo (SPGR) technique for whole-heart water–fat imaging at 3 Tesla (T). Methods We developed a three-dimensional (3D) multi-echo SPGR pulse sequence with electrocardiographic gating and navigator echoes and evaluated its performance at 3T in healthy volunteers (N = 6) and patients (N = 20). CSE-SPGR, 3D SPGR, and 3D balanced-SSFP with chemical fat saturation were compared in six healthy subjects with images evaluated for overall image quality, level of residual artifacts, and quality of fat suppression. A similar scoring system was used for the patient datasets. Results Images of diagnostic quality were acquired in all but one subject. CSE-SPGR performed similarly to SPGR with fat saturation, although it provided a more uniform fat suppression over the whole field of view. Balanced-SSFP performed worse than SPGR-based methods. In patients, CSE-SPGR produced excellent fat suppression near metal. Overall image quality was either good (7/20) or excellent (12/20) in all but one patient. There were significant artifacts in 5/20 clinical cases. Conclusion CSE-SPGR is a promising technique for whole-heart water–fat imaging during free-breathing. The robust fat suppression in the water-only image could improve assessment of complex morphology at 3T and in the presence of off-resonance, with additional information contained in the fat-only image. Magn Reson Med 72:718–725, 2014. © 2013 Wiley Periodicals, Inc.

Purpose To characterize the confounding effect of temperature on chemical shift-encoded (CSE) fat quantification. Methods The proton resonance frequency of water, unlike triglycerides, depends on temperature. This leads to a temperature dependence of the spectral models of fat (relative to water) that are commonly used by CSE-MRI methods. Simulation analysis was performed for 1.5 Tesla CSE fat–water signals at various temperatures and echo time combinations. Oil–water phantoms were constructed and scanned at temperatures between 0 and 40°C using spectroscopy and CSE imaging at three echo time combinations. An explanted human liver, rejected for transplantation due to steatosis, was scanned using spectroscopy and CSE imaging. Fat–water reconstructions were performed using four different techniques: magnitude and complex fitting, with standard or temperature-corrected signal modeling. Results In all experiments, magnitude fitting with standard signal modeling resulted in large fat quantification errors. Errors were largest for echo time combinations near TEinit ≈ 1.3 ms, ΔTE ≈ 2.2 ms. Errors in fat quantification caused by temperature-related frequency shifts were smaller with complex fitting, and were avoided using a temperature-corrected signal model. Conclusion Temperature is a confounding factor for fat quantification. If not accounted for, it can result in large errors in fat quantifications in phantom and ex vivo acquisitions. Magn Reson Med 72:464–470, 2014. © 2013 Wiley Periodicals, Inc.

Imaging using high channel-count coil arrays can benefit a broad range of clinical applications through improved signal-to-noise ratio (SNR), higher parallel imaging acceleration factors and increased anatomical coverage (1–3). However, maintaining clinically acceptable reconstruction times can be challenging when using high channel-count coil arrays. A variety of approaches have been explored to improve the efficiency of reconstruction algorithms for high channel-count imaging (4–14). Many of these techniques, including this work, have focused on combining or reducing the effective number of channels earlier in the reconstruction pipeline. In this way, the computational burden on subsequent steps in the reconstruction process is lessened. Channel combination methods can be categorized based on the domain in which channel combination is performed: image-space, time-domain or k-space. Image-space channel combination methods are widely used due to their ability to optimize final image SNR and their ease of use (15). However, image-space solutions can be computationally and memory intensive for high channel-count coil arrays, since channel combination must take place relatively late in the reconstruction pipeline. At the other end of the spectrum, time-domain channel combination (4) has received significant attention. Time-domain channel combination performs channel combination independently at each acquisition time point—at the beginning of the reconstruction pipeline. Time-domain channel combination is very effective in reducing the computation and memory requirements for the image reconstruction pipeline. The weaknesses of time-domain channel combination are (1) SNR can be degraded, sometimes significantly (16) and (2) phase cancellation artifacts are often unavoidable for some coil geometries (5). As a result, time-domain channel combination is not widely used to combine all receiver channels into a single channel data stream. Instead, the approach is typically used to reduce the channel-count significantly but without appreciably degrading image quality (6–12). Methods that take this approach are often referred to as either “array compression” or “coil selection” depending on whether or not they combine channel data streams during the channel reduction. Because these approaches do not output a single channel data set, they must be paired with another channel combination method later in the reconstruction pipeline. In this way, these approaches are complementary to other channel combination strategies, including image-space and k-space approaches (13,14). In comparison to image-space channel combination and time-domain channel combination, k-space channel combination has received relatively less attention. k-Space channel combination can be performed by convolving the k-space data for each channel with its own k-space convolution kernel and summing across channels to create a single or reduced number of k-space data sets. Unlike time-domain channel combination, it is challenging to implement k-space channel combination in hardware as the convolution coefficients are dependent on the k-space sampling strategy. Unlike image-space channel combination, k-space channel combination is unable to optimize SNR independently at every pixel location. However, k-space channel combination does have important advantages: it has more degrees of freedom compared to time-domain channel combination that allow it to achieve better SNR and it can be performed earlier in the reconstruction pipeline compared to image-space channel combination, potentially improving reconstruction efficiency. Early work in k-space channel combination was carried out as part of parallel imaging reconstruction methods. Methods such as SMASH, AUTO-SMASH and VD-AUTO-SMASH combine the parallel imaging unaliasing operation and the channel combination operation into a single step, both in the generation and application of reconstruction coefficients (17–19). Two challenges for these methods are that the SNR of the final combined images can be sub-optimal and they are prone to phase cancellation artifacts (20). Both of these issues can be attributed to sub-optimal channel combination. The GRAPPA method improved on prior k-space parallel imaging methods by separating the unaliasing operation from the channel combination operation and performing channel combination in image-space (20). While this approach has been very successful, it does lead to an increased computational burden, since the unaliasing operation in GRAPPA scales as the square of the number of channels. There is also a large memory requirement as separate data sets for each channel are formed in image-space. As the number of channels grows, a “channel-by-channel” approach becomes increasingly difficult to perform in clinically acceptable reconstruction times. The problem is exacerbated by the clinical motivations for moving to higher channel-counts: acquiring larger image matrices, and the use of more temporal phases for dynamic contrast enhanced imaging. For example, moving from a single phase eight-channel 256 × 256 × 64 acquisition to a 20 phase 32-channel 320 × 320 × 128 acquisition results in a 1000-fold increase in computation for the unaliasing operation of channel-by-channel parallel imaging with image-space channel combination. This increased computational load can be dealt with using both improvements in computing hardware and algorithmic improvements. Using more powerful reconstruction hardware without algorithmic changes has the advantage that this approach poses no risk to altering the image quality. In contrast, algorithmic changes can modify and potentially degrade image quality. However, hardware solutions can be more costly to roll out to a large installed base compared to software solutions. With such large potential increases in computation, it is likely that improvements in both computing hardware and algorithms will be needed. Because of this, it is important that improved algorithms work well with powerful hardware, which for the foreseeable future means that the algorithms must be amenable to parallel computing architectures. This work is motivated by a desire to reduce the computational demands for high channel-count image reconstruction while retaining image quality and supporting sampling schemes acquiring irregularly spaced k-space points on a Cartesian grid. Irregularly spaced sampling schemes used in the experiments in this work consist of the inclusion of internal calibration lines in the reconstruction and the use of variable sample spacing (e.g., acquire two, skip one or skip one, acquire one, skip two to create sampling reductions, R, of 1.5 and 2.5 respectively). The purpose of this work is to describe and evaluate a new method for designing local k-space channel combination kernels and integrating them with parallel imaging. We refer to the approach as the direct virtual coil (DVC) method (21). This work focuses on describing the technical methodology for DVC and relies on separate works to discuss specific clinical applications (22).

Purpose MR-based quantification of liver magnetic susceptibility may enable field strength-independent measurement of liver iron concentration (LIC). However, susceptibility quantification is challenging, due to nonlocal effects of susceptibility on the B0 field. The purpose of this work is to demonstrate feasibility of susceptibility-based LIC quantification using a fat-referenced approach. Methods Phantoms consisting of vials with increasing iron concentrations immersed between oil/water layers, and 27 subjects (9 controls/18 subjects with liver iron overload) were scanned. Ferriscan (1.5 T) provided R2-based reference LIC. Multiecho three-dimensional-SPGR (1.5 T/3 T) enabled fat-water, B0- and R2*-mapping. Phantom iron concentration (mg Fe L−1) was estimated from B0 differences (ΔB0) between vials and neighboring oil. Liver susceptibility and LIC (mg Fe g−1 dry tissue) was estimated from ΔB0 between the lateral right lobe of the liver and adjacent subcutaneous adipose tissue. Results Estimated phantom iron concentrations had good correlation with true iron concentrations (1.5 T:slope = 0.86, intercept = 0.72, r2 = 0.98; 3 T:slope = 0.85, intercept = 1.73, r2 = 0.98). In liver, ΔB0 correlated strongly with R2* (1.5 T:r2 = 0.86; 3 T:r2 = 0.93) and B0-LIC had good agreement with Ferriscan-LIC (slopes/intercepts nearly 1.0/0.0, 1.5 T:r2 = 0.67, slope = 0.93 ± 0.13, P ≈ 0.50, intercept = 1.93 ± 0.78, P ≈ 0.02; 3 T:r2 = 0.84, slope = 1.01 ± 0.09, P ≈ 0.90, intercept = 0.23 ± 0.52, P ≈ 0.68). Discussion Fat-referenced, susceptibility-based LIC estimation is feasible at both field strengths. This approach may enable improved susceptibility mapping in the abdomen. Magn Reson Med 70:648–656, 2013. © 2013 Wiley Periodicals, Inc.

Purpose Detection, characterization, and monitoring of hepatocellular carcinomas (HCC) in patients with cirrhosis is challenging due to their variable and rapid arterial enhancement. Multiphase dynamic contrast-enhanced MRI (CE-MRI) is used clinically for HCC assessment, but suffers from limited temporal resolution and difficulty in coordinating imaging and breath-hold timing within a narrow temporal window of interest. We demonstrate a volumetric, high spatial resolution, high temporal resolution dynamic contrast enhanced liver imaging method for improved detection and characterization of HCC.

Radial trajectories facilitate high-resolution balanced steady state free precession (bSSFP) because the efficient gradients provide more time to extend the trajectory in k-space. A number of radial bSSFP methods that support fat-water separation have been developed; however, most of these methods require an environment with limited B0 inhomogeneity. In this work, high-resolution bSSFP with fat-water separation is achieved in more challenging B0 environments by combining a 3D radial trajectory with the IDEAL chemical species separation method. A method to maintain very high resolution within the timing constraints of bSSFP and IDEAL is described using a dual-pass pulse sequence. The sampling of a unique set of radial lines at each echo time is investigated as a means to circumvent the longer scan time that IDEAL incurs as a multiecho acquisition. The manifestation of undersampling artifacts in this trajectory and their effect on chemical species separation are investigated in comparison to the case in which each echo samples the same set of radial lines. This new bSSFP method achieves 0.63 mm isotropic resolution in a 5-min scan and is demonstrated in difficult in vivo imaging environments, including the breast and a knee with ACL reconstruction hardware at 1.5 T.

Purpose To develop and test the feasibility of a spectrally resolved fully phase-encoded (SR-FPE) three-dimensional fast spin-echo technique and to demonstrate its application for distortion-free imaging near metal and chemical species separation. Methods In separate scans at 1.5 T, a hip prosthesis phantom and a sphere filled with gadolinium solution were imaged with SR-FPE and compared to conventional three-dimensional-fast spin-echo. Spectral modeling was performed on the SR-FPE data to generate the following parametric maps: species-specific signal (ρspecies), B0 field inhomogeneity, and R*2. The prosthesis phantom was also scanned using a 16-channel coil at 1.5 T. The fully sampled k-space data were retrospectively undersampled to demonstrate the feasibility of parallel imaging acceleration in all three phase-encoding directions, in combination with corner-cutting and half-Fourier sampling. Finally, SR-FPE was performed with an acetone/water/oil phantom to test chemical species separation. Results High quality distortion-free images and parametric maps were generated from SR-FPE. A 4 h SR-FPE scan was retrospectively accelerated to 12 min while preserving spectral information and 7.5 min without preserving spectral data. Chemical species separation was demonstrated in the acetone/water/oil phantom. Conclusion This work demonstrates the feasibility of SR-FPE to perform chemical species separation and spectrally resolved imaging near metal without distortion, in scan times appropriate for the clinical setting. Magn Reson Med 71:681–690, 2014. © 2013 Wiley Periodicals, Inc.

Purpose To demonstrate the feasibility of direct virtual coil (DVC) in the setting of 4D dynamic imaging used in multiple clinical applications. Theory and Methods Three dynamic imaging applications were chosen: pulmonary perfusion, liver perfusion, and peripheral MR angiography (MRA), with 18, 11, and 10 subjects, respectively. After view-sharing, the k-space data were reconstructed twice: once with channel-by-channel (CBC) followed by sum-of-squares coil combination and once with DVC. Images reconstructed using CBC and DVC were compared and scored based on overall image quality by two experienced radiologists using a five-point scale. Results The CBC and DVC showed similar image quality in image domain. Time course measurements also showed good agreement in the temporal domain. CBC and DVC images were scored as equivalent for all pulmonary perfusion cases, all liver perfusion cases, and four of the 10 peripheral MRA cases. For the remaining six peripheral MRA cases, DVC were scored as slightly better (not clinically significant) than the CBC images by Radiologist A and as equivalent by Radiologist B. Conclusion For dynamic contrast-enhanced MR applications, it is clinically feasible to reduce image reconstruction time while maintaining image quality and time course measurement using the DVC technique. Magn Reson Med 71:783–789, 2014. © 2013 Wiley Periodicals, Inc.

To develop an externally calibrated parallel imaging technique for three-dimensional multispectral imaging (3D-MSI) in the presence of metallic implants.A fast, ultrashort echo time (UTE) calibration acquisition is proposed to enable externally calibrated parallel imaging techniques near metallic implants. The proposed calibration acquisition uses a broadband radiofrequency (RF) pulse to excite the off-resonance induced by the metallic implant, fully phase-encoded imaging to prevent in-plane distortions, and UTE to capture rapidly decaying signal. The performance of the externally calibrated parallel imaging reconstructions was assessed using phantoms and in vivo examples.Phantom and in vivo comparisons to self-calibrated parallel imaging acquisitions show that significant reductions in acquisition times can be achieved using externally calibrated parallel imaging with comparable image quality. Acquisition time reductions are particularly large for fully phase-encoded methods such as spectrally resolved fully phase-encoded three-dimensional (3D) fast spin-echo (SR-FPE), in which scan time reductions of up to 8 min were obtained.A fully phase-encoded acquisition with broadband excitation and UTE enabled externally calibrated parallel imaging for 3D-MSI, eliminating the need for repeated calibration regions at each frequency offset. Significant reductions in acquisition time can be achieved, particularly for fully phase-encoded methods like SR-FPE. Magn Reson Med 77:2303-2309, 2017. © 2016 International Society for Magnetic Resonance in Medicine.

Fat suppression is an essential part of routine MRI scanning. Multiecho chemical-shift based water-fat separation methods estimate and correct for Bo field inhomogeneity. However, they must contend with the intrinsic challenge of water-fat ambiguity that can result in water-fat swapping. This problem arises because the signals from two chemical species, when both are modeled as a single discrete spectral peak, may appear indistinguishable in the presence of Bo off-resonance. In conventional methods, the water-fat ambiguity is typically removed by enforcing field map smoothness using region growing based algorithms. In reality, the fat spectrum has multiple spectral peaks. Using this spectral complexity, we introduce a novel concept that identifies water and fat for multiecho acquisitions by exploiting the spectral differences between water and fat. A fat likelihood map is produced to indicate if a pixel is likely to be water-dominant or fat-dominant by comparing the fitting residuals of two different signal models. The fat likelihood analysis and field map smoothness provide complementary information, and we designed an algorithm (Fat Likelihood Analysis for Multiecho Signals) to exploit both mechanisms. It is demonstrated in a wide variety of data that the Fat Likelihood Analysis for Multiecho Signals algorithm offers highly robust water-fat separation for 6-echo acquisitions, particularly in some previously challenging applications.

For MR applications such as contrast-enhanced MR angiography, it is desirable to achieve simultaneously high spatial and temporal resolution. The current clinical standard uses view-sharing methods combined with parallel imaging; however, this approach still provides limited spatial and temporal resolution. To improve on the clinical standard, we present an interleaved variable density (IVD) sampling method that pseudorandomly undersamples each individual frame of a 3D Cartesian ky–kz plane combined with parallel imaging acceleration. From this dataset, time-resolved images are reconstructed with a method that combines parallel imaging with a multiplicative constraint. Total acceleration factors on the order of 20 are achieved for contrast-enhanced MR angiography of the lower extremities, and improvements in temporal fidelity of the depiction of the contrast bolus passage are demonstrated relative to the clinical standard. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.

Multipoint water-fat separation techniques rely on different water-fat phase shifts generated at multiple echo times to decompose water and fat. Therefore, these methods require complex source images and allow unambiguous separation of water and fat signals. However, complex-based water-fat separation methods are sensitive to phase errors in the source images, which may lead to clinically important errors. An alternative approach to quantify fat is through "magnitude-based" methods that acquire multiecho magnitude images. Magnitude-based methods are insensitive to phase errors, but cannot estimate fat-fraction greater than 50%. In this work, we introduce a water-fat separation approach that combines the strengths of both complex and magnitude reconstruction algorithms. A magnitude-based reconstruction is applied after complex-based water-fat separation to removes the effect of phase errors. The results from the two reconstructions are then combined. We demonstrate that using this hybrid method, 0-100% fat-fraction can be estimated with improved accuracy at low fat-fractions.

Noninvasive biomarkers of intracellular accumulation of fat within the liver (hepatic steatosis) are urgently needed for detection and quantitative grading of nonalcoholic fatty liver disease, the most common cause of chronic liver disease in the United States. Accurate quantification of fat with MRI is challenging due the presence of several confounding factors, including T z.ast;2 decay. The specific purpose of this work is to quantify the impact of Tz.ast;2decay and develop a multiexponential Tz.ast;2 correction method for improved accuracy of fat quantification, relaxing assumptions made by previous T z.ast;2 correction methods. A modified Gauss-Newton algorithm is used to estimate the Tz.ast;2 for water and fat independently. Improved quantification of fat is demonstrated, with independent estimation of Tz.ast;2 for water and fat using phantom experiments. The tradeoffs in algorithm stability and accuracy between multiexponential and single exponential techniques are discussed. © 2010 Wiley-Liss, Inc.

Tissues containing both water and lipids, e.g., breast, confound standard MR proton reference frequency-shift methods for mapping temperatures due to the lack of temperature-induced frequency shift in lipid protons. Generalized Dixon chemical shift-based water-fat separation methods, such as GE's iterative decomposition of water and fat with echo asymmetry and least-squares estimation method, can result in complex water and fat images. Once separated, the phase change over time of the water signal can be used to map temperature. Phase change of the lipid signal can be used to correct for non-temperature-dependent phase changes, such as amplitude of static field drift. In this work, an image acquisition and postprocessing method, called water and fat thermal MRI, is demonstrated in phantoms containing 30:70, 50:50, and 70:30 water-to-fat by volume. Noninvasive heating was applied in an Off1-On-Off2 pattern over 50 min, using a miniannular phased radiofrequency array. Temperature changes were referenced to the first image acquisition. Four fiber optic temperature probes were placed inside the phantoms for temperature comparison. Region of interest (ROI) temperature values colocated with the probes showed excellent agreement (global mean +/- standard deviation: -0.09 +/- 0.34 degrees C) despite significant amplitude of static field drift during the experiments.

Multiecho sequences provide an efficient means to acquire multiple echoes in a single repetition, which has found applications in spectroscopy, relaxometry, and water-fat separation. By replacing the fly-back gradients in unipolar multiecho sequences with alternating readout gradients, bipolar multiecho sequences greatly reduce both echo-spacing and repetition interval. This offers many attractive advantages, such as shorter scan times, higher SNR efficiency, more robust field map estimation, reduced motion-induced artifacts, and less sensitivity to short T(2)*. However, the alternating readout gradients cause several technical problems, including delay effects and image misregistrations, which prevent direct application of existing water-fat separation methods. This work presents solutions to address these problems, including a post-processing method that shifts k-space data to correct k-space echo misalignment, an image warping method that utilizes a low-resolution field map to remove field-inhomogeneity-induced misregistration, and a k-space water-fat separation method that eliminates chemical-shift-induced artifacts in separated water and fat images. In addition, a noise amplification factor, which characterizes the noise present in separated images, is proposed to serve as a useful guideline for choosing imaging parameters or regularization parameters in the case of ill-conditioned separation. The proposed methods are validated both in phantoms and in vivo to enable reliable and SNR efficient water-fat separation with bipolar multiecho sequences.