Two‐point dixon method with flexible echo times

The two‐point Dixon method is a proton chemical shift imaging technique that produces separated water‐only and fat‐only images from a dual‐echo acquisition. It is shown how this can be achieved without the usual constraints on the echo times. A signal model considering spectral broadening of the fat peak is proposed for improved water/fat separation. Phase errors, mostly due to static field inhomogeneity, must be removed prior to least‐squares estimation of water and fat. To resolve ambiguity of the phase errors, a corresponding global optimization problem is formulated and solved using a message‐passing algorithm. It is shown that the noise in the water and fat estimates matches the Cramér‐Rao bounds, and feasibility is demonstrated for in vivo abdominal breath‐hold imaging. The water‐only images were found to offer superior fat suppression compared with conventional spectrally fat suppressed images. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Fast dixon‐based multisequence and multiplanar MRI for whole‐body detection of cancer metastases

Purpose

To develop and demonstrate the feasibility of multisequence and multiplanar MRI for whole‐body cancer detection.

Materials and Methods

Two fast Dixon‐based sequences and a diffusion‐weighted sequence were used on a commercially available 1.5 T scanner for whole‐body cancer detection. The study enrolled 19 breast cancer patients with known metastases and in multistations acquired whole‐body axial diffusion‐weighted, coronal T2‐weighted, axial/sagittal pre‐ and postcontrast T1‐weighted, as well as triphasic abdomen images. Three radiologists subjectively scored Dixon images of each series for overall image quality and fat suppression uniformity on a 4‐point scale (1 = poor, 2 = fair, 3 = good, and 4 = excellent).

Results

Eighteen of the 19 patients completed the whole‐body MRI successfully. The mean acquisition time and overall patient table time were 46 ± 3 and 69 ± 5 minutes, respectively. The average radiologists' scores for overall image quality and fat suppression uniformity were both 3.4 ± 0.5. The image quality was consistent between patients and all completed whole‐body examinations were diagnostically adequate.

Conclusion

Whole‐body MRI offering essentially all the most optimal tumor‐imaging sequences in a typical 1‐hour time slot can potentially become an appealing “one‐stop‐shop” for whole‐body cancer imaging. J. Magn. Reson. Imaging 2009;29:1154–1162. © 2009 Wiley‐Liss, Inc.     

Fat‐water separated delayed hyperenhanced myocardial infarct imaging

Fat deposition associated with myocardial infarction (MI) has been reported as a commonly occurring phenomenon. Magnetic resonance imaging (MRI) has the ability to efficiently detect MI using T₁‐sensitive contrast‐enhanced sequences and fat via its resonant frequency shift. In this work, the feasibility of fat‐water separation applied to the conventional delayed hyperenhanced (DHE) MI imaging technique is demonstrated. A three‐point Dixon acquisition and reconstruction was combined with an inversion recovery gradient‐echo pulse sequence. This allowed fat‐water separation along with T₁ sensitive imaging after injection of a gadolinium contrast agent. The technique is demonstrated in phantom experiments and three subjects with chronic MI. Areas of infarction were well defined as conventional hyperenhancement in water images. In two cases, fatty deposition was detected in fat images and confirmed by precontrast opposed‐phase imaging. Magn Reson Med 60:503–509, 2008. © 2008 Wiley‐Liss, Inc.     

Myocardial fat quantification in humans: Evaluation by two‐point water‐fat imaging and localized proton spectroscopy

Proton MR spectroscopy (¹H‐MRS) has been used for in vivo quantification of intracellular triglycerides within the sarcolemma. The purpose of this study was to assess whether breath‐hold dual‐echo in‐ and out‐of‐phase MRI at 3.0 T can quantify the fat content of the myocardium. Biases, including T₁, T*₂, and noise, that confound the calculation of the fat fraction were carefully corrected. Thirty‐four of 46 participants had both MRI and MRS data. The fat fractions from MRI showed a strong correlation with fat fractions from MRS (r = 0.78; P < 0.05). The mean myocardial fat fraction for all 34 subjects was 0.7 ± 0.5% (range: 0.11–3%) assessed with MRS and 1.04 ± 0.4% (range: 0.32–2.44%) assessed with in‐ and out‐of‐phase MRI (P < 0.05). Scanning times were less than 15 sec for Dixon imaging, plus an additional minute for the acquisition used for T*₂ calculation, and 15‐20 min for MRS. The average postprocessing time for MRS was 3 min and 5 min for MRI including T*₂ measurement. We conclude that the dual echo method provides a rapid means to detect and quantifying myocardial fat content in vivo. Correction/adjustment for field inhomogeneity using three or more echoes seems crucial for the dual echo approach. Magn Reson Med 63:892–901, 2010. © 2010 Wiley‐Liss, Inc.     

In vivo high‐resolution magnetic resonance skin imaging at 1.5 T and 3 T

As a noninvasive modality, MR is attractive for in vivo skin imaging. Its unique soft tissue contrast makes it an ideal imaging modality to study the skin water content and to resolve the different skin layers. In this work, the challenges of in vivo high‐resolution skin imaging are addressed. Three 3D Cartesian sequences are customized to achieve high‐resolution imaging and their respective performance is evaluated. The balanced steady‐state free precession (bSSFP) and gradient echo (GRE) sequences are fast but can be sensitive to off‐resonance artifacts. The fast large‐angle spin echo (FLASE) sequence provides a sharp depiction of the hypodermis structures but results in more specific absorption rate (SAR). The effect of increasing the field strength is assessed. As compared to 1.5 T, signal‐to‐noise ratio at 3 T slightly increases in the hypodermis and almost doubles in the dermis. The need for fat/water separation is acknowledged and a solution using an interleaved three‐point Dixon method and an iterative reconstruction is shown to be effective. The effects of motion are analyzed and two techniques to prevent motion and correct for it are evaluated. Images with 117 × 117 × 500 μm³ resolution are obtained in imaging times under 6 min. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Two‐point dixon technique provides robust fat suppression for multi‐mouse imaging

Purpose:

To determine whether Dixon‐based fat separation techniques can provide more robust removal of lipid signals from multiple‐mouse magnetic resonance imaging (MRI)‐acquired images than conventional frequency selective chemical saturation techniques.

Materials and Methods:

A two‐point Dixon technique was implemented using a RARE‐based pulse sequence and techniques for multivolume fat suppression were evaluated using a 4‐element array of volume resonators at 4.7 T. Images were acquired of both phantoms and mice.

Results:

Fat saturation was achieved on all four channels of the multiple mouse acquisition with the Dixon technique, while failures of fat saturation were found with chemical saturation techniques.

Conclusion:

This proof of concept study found that Dixon fat separation provided more reliable and homogenous fat suppression than chemical saturation in phantoms and in vivo. J. Magn. Reson. Imaging 2010; 31:510–514. © 2010 Wiley‐Liss, Inc.     

Whole‐heart contrast‐enhanced coronary magnetic resonance angiography using gradient echo interleaved EPI

Whole‐heart coronary MR angiography (MRA) is a promising method for detecting coronary artery disease. However, the imaging time is relatively long (on the order of 10–15 min). Such a long imaging time may result in patient discomfort and compromise the robustness of whole‐heart coronary MRA due to increased respiratory and cardiac motion artifacts. The goal of this study was to optimize a gradient echo interleaved echo planar imaging (GRE‐EPI) acquisition scheme for reducing the imaging time of contrast‐enhanced whole‐heart coronary MRA. Numerical simulations and phantom studies were used to optimize the GRE‐EPI sequence parameters. Healthy volunteers were scanned with both the proposed GRE‐EPI sequence and a 3D TrueFISP sequence for comparison purposes. Slow infusion (0.5 cc/sec) of Gd‐DTPA was used to enhance the signal‐to‐noise ratio (SNR) of the GRE‐EPI acquisition. Whole‐heart images with the GRE‐EPI technique were acquired with a true resolution of 1.0 × 1.1 × 2.0 mm³ in an average scan time of 4.7 ± 0.7 min with an average navigator efficiency of 44 ± 6%. The GRE‐EPI acquisition showed excellent delineation of all the major coronary arteries with scan time reduced by a factor of 2 compared with the TrueFISP acquisition. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

T1‐weighted 3D dynamic contrast‐enhanced MRI of the breast using a dual‐echo dixon technique at 3 T

Purpose:

To evaluate a single‐pass fast spoiled gradient echo (FSPGR) two‐point Dixon sequence and a gradient echo sequence with spectral fat suppression in their performance at 3 T for fat suppressed contrast‐enhanced bilateral breast imaging.

Materials and Methods:

Twenty patients were prospectively enrolled in an imaging protocol that included axial Dixon and 3D FSPGR with spectrally selective fat saturation sequences as part of patient care in this study. Qualitative analysis was performed retrospectively by two readers who scored the images for homogeneity and degree of fat saturation, severity of artifacts, and quality of normal anatomical structures. Enhancing lesions were scored according to the confidence with which American College of Radiology (ACR) BI‐RADS magnetic resonance imaging (MRI) features were identified.

Results:

The Dixon sequence showed superior fat saturation homogeneity, quality of posterior anatomical structures, and decreased artifact severity that were statistically significant (P < 0.0001). The degree of fat saturation was scored higher in the Dixon sequence, although the difference did not reach statistical significance. There were no significant differences between the 3D T1‐weighted FSPGR and Dixon groups for assessing lesion features.

Conclusion:

Our findings suggest that the Dixon technique is an effective fat suppression method for contrast‐enhanced breast MRI. The Dixon technique also seemed to provide better anatomical definition of posterior structures and improvement in severity of artifacts. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Time‐resolved bolus‐chase MR angiography with real‐time triggering of table motion

Time‐resolved bolus‐chase contrast‐enhanced MR angiography with real‐time station switching is demonstrated. The Cartesian acquisition with projection reconstruction‐like sampling (CAPR) technique and high 2D sensitivity encoding (SENSE) (6× or 8×) and 2D homodyne (1.8×) accelerations were used to acquire 3D volumes with 1.0‐mm isotropic spatial resolution and frame times as low as 2.5 sec in two imaging stations covering the thighs and calves. A custom real‐time system was developed to reconstruct and display CAPR frames for visually guided triggering of table motion upon passage of contrast through the proximal station. The method was evaluated in seven volunteers. High‐spatial‐resolution arteriograms with minimal venous contamination were consistently acquired in both stations. Real‐time stepping table contrast‐enhanced MR angiography is a method for providing time‐resolved images with high spatial resolution over an extended field‐of‐view. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

High‐resolution spiral imaging on a whole‐body 7T scanner with minimized image blurring

High‐resolution (～0.22 mm) images are preferably acquired on whole‐body 7T scanners to visualize minianatomic structures in human brain. They usually need long acquisition time (～12 min) in three‐dimensional scans, even with both parallel imaging and partial Fourier samplings. The combined use of both fast imaging techniques, however, leads to occasionally visible undersampling artifacts. Spiral imaging has an advantage in acquisition efficiency over rectangular sampling, but its implementations are limited due to image blurring caused by a strong off‐resonance effect at 7T. This study proposes a solution for minimizing image blurring while keeping spiral efficient. Image blurring at 7T was, first, quantitatively investigated using computer simulations and point‐spread functions. A combined use of multishot spirals and ultrashort echo time acquisitions was then employed to minimize off‐resonance‐induced image blurring. Experiments on phantoms and healthy subjects were performed on a whole‐body 7T scanner to show the performance of the proposed method. The three‐dimensional brain images of human subjects were obtained at echo time = 1.18 ms, resolution = 0.22mm (field of view = 220mm, matrix size = 1024), and in‐plane spiral shots = 128, using a home‐developed ultrashort echo time sequence (acquisition‐weighted stack of spirals). The total acquisition time for 60 partitions at pulse repetition time = 100 ms was 12.8 min without use of parallel imaging and partial Fourier sampling. The blurring in these spiral images was minimized to a level comparable to that in gradient‐echo images with rectangular acquisitions, while the spiral acquisition efficiency was maintained at eight. These images showed that spiral imaging at 7T was feasible. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Contrast‐enhanced whole‐heart coronary magnetic resonance angiography at 3 T with radial EPI

Whole‐heart coronary magnetic resonance angiography is a promising method for detecting coronary artery disease. However, the imaging time is relatively long (typically 10–15 min). The goal of this study was to implement a radial echo planar imaging sequence for contrast‐enhanced whole‐heart coronary magnetic resonance angiography, with the aim of combining the scan efficiency of echo planar imaging with the motion insensitivity of radial k‐space sampling. A self‐calibrating phase correction technique was used to correct for off‐resonance effects, trajectory measurement was used to correct for k‐space trajectory errors, and variable density sampling was used in the partition direction to reduce streaking artifacts. Seven healthy volunteers and two patients were scanned with the proposed radial echo planar imaging sequence, and the images were compared with a traditional gradient echo and X‐ray angiography techniques, respectively. Whole‐heart images with the radial EPI technique were acquired with a resolution of 1.0 × 1.0 × 2.0 mm³ in a scan time of 5 min. In healthy volunteers, the average image quality scores and visualized vessel lengths of the RCA and LAD were similar for the radial EPI and gradient echo techniques (P value > 0.05 for all). Anecdotal patient studies showed excellent agreement of the radial EPI technique with X‐ray angiography. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Noninvasive temperature mapping with MRI using chemical shift water‐fat separation

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°C) despite significant amplitude of static field drift during the experiments. Magn Reson Med 63:1238–1246, 2010. © 2010 Wiley‐Liss, Inc.     

T1 independent,T2* corrected MRI with accurate spectral modeling for quantification of fat: Validation in a fat‐water‐SPIO phantom

Purpose:

To validate a T₁‐independent, T₂*‐corrected fat quantification technique that uses accurate spectral modeling of fat using a homogeneous fat‐water‐SPIO phantom over physiologically expected ranges of fat percentage and T₂* decay in the presence of iron overload.

Materials and Methods:

A homogeneous gel phantom consisting of vials with known fat‐fractions and iron concentrations is described. Fat‐fraction imaging was performed using a multiecho chemical shift‐based fat‐water separation method (IDEAL), and various reconstructions were performed to determine the impact of T₂* correction and accurate spectral modeling. Conventional two‐point Dixon (in‐phase/out‐of‐phase) imaging and MR spectroscopy were performed for comparison with known fat‐fractions.

Results:

The best agreement with known fat‐fractions over the full range of iron concentrations was found when T₂* correction and accurate spectral modeling were used. Conventional two‐point Dixon imaging grossly underestimated fat‐fraction for all T₂* values, but particularly at higher iron concentrations.

Conclusion:

This work demonstrates the necessity of T₂* correction and accurate spectral modeling of fat to accurately quantify fat using MRI. J. Magn. Reson. Imaging 2009;30:1215–1222. © 2009 Wiley‐Liss, Inc.     

Multiplex RARE: A simultaneous multislice spin‐echo sequence that fulfils CPMG conditions

This work presents a new imaging sequence in which multiple slices are simultaneously excited and refocused in a spin‐echo train. The multiple spin‐echo trains are interleaved in such a manner that (i) the Carr‐Purcell‐Meiboom‐Gill conditions are fulfilled at all times, and (ii) the signals from slices can be separated, preventing aliasing. This paper also demonstrates how the sequence may be used in a novel fat‐water Dixon method that enables fast volume coverage. The technique is demonstrated in phantoms and in vivo. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Dual‐echo Dixon imaging with flexible choice of echo times

In this work, a new two‐point method for water–fat imaging is described and explored. It generalizes existing two‐point methods by eliminating some of the restrictions that these methods impose on the choice of echo times. Thus, the new two‐point method promises to provide more freedom in the selection of protocol parameters and to reach higher scan efficiency. Its performance was studied theoretically and was evaluated experimentally in abdominal imaging with a multigradient‐echo sequence. While depending on the choice of echo times, it is generally found to be favorable compared to existing two‐point methods. Notably, water images with higher spatial resolution and better signal‐to‐noise ratio were attained with it in single breathholds at 3.0 T and 1.5 T, respectively. The use of more accurate spectral models of fat is shown to substantially reduce observed variations in the extent of fat suppression. The acquisition of in‐ and opposed‐phase images is demonstrated to be replaceable by a synthesis from water and fat images. The new two‐point method is finally also applied to autocalibrate a multidimensional eddy current correction and to enhance the fat suppression achieved with three‐point methods in this way, especially toward the edges of larger field of views. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

A simple low‐SAR technique for chemical‐shift selection with high‐field spin‐echo imaging

We have discovered a simple and highly robust method for removal of chemical shift artifact in spin‐echo MR images, which simultaneously decreases the radiofrequency power deposition (specific absorption rate). The method is demonstrated in spin‐echo echo‐planar imaging brain images acquired at 7 T, with complete suppression of scalp fat signal. When excitation and refocusing pulses are sufficiently different in duration, and thus also different in the amplitude of their slice‐select gradients, a spatial mismatch is produced between the fat slices excited and refocused, with no overlap. Because no additional radiofrequency pulse is used to suppress fat, the specific absorption rate is significantly reduced compared with conventional approaches. This enables greater volume coverage per unit time, well suited for functional and diffusion studies using spin‐echo echo‐planar imaging. Moreover, the method can be generally applied to any sequence involving slice‐selective excitation and at least one slice‐selective refocusing pulse at high magnetic field strengths. The method is more efficient than gradient reversal methods and more robust against inhomogeneities of the static (polarizing) field (B₀). Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Multiecho time‐resolved acquisition (META): A high spatiotemporal resolution dixon imaging sequence for dynamic contrast‐enhanced MRI

Purpose

To evaluate a new dynamic contrast‐enhanced (DCE) imaging technique called multiecho time‐resolved acquisition (META) for abdominal/pelvic imaging. META combines an elliptical centric time‐resolved three‐dimensional (3D) spoiled gradient‐recalled echo (SPGR) imaging scheme with a Dixon‐based fat‐water separation algorithm to generate high spatiotemporal resolution volumes.

Materials and Methods

Twenty‐three patients referred for hepatic metastases or renal masses were imaged using the new META sequence and a conventional fat‐suppressed 3D SPGR sequence on a 3T scanner. In 12 patients, equilibrium‐phase 3D SPGR images acquired immediately after META were used for comparing the degree and homogeneity of fat suppression, artifacts, and overall image quality. In the remaining 11 of 23 patients, DCE 3D SPGR images acquired in a previous or subsequent examination were used for comparing the efficiency of arterial phase capture in addition to the qualitative analysis for the degree and homogeneity of fat suppression, artifacts, and overall image quality.

Results

META images were determined to be significantly better than conventional 3D SPGR images for degree and uniformity of fat suppression and ability to visualize the arterial phase. There were no significant differences in artifact levels or overall image quality.

Conclusion

META is a promising high spatiotemporal resolution imaging sequence for capturing the fast dynamics of hyperenhancing hepatic lesions and provides robust fat suppression even at 3T. J. Magn. Reson. Imaging 2009. © 2009 Wiley‐Liss, Inc.     

T2‐weighted 3D fast spin echo imaging with water–fat separation in a single acquisition

Purpose:

To develop a robust 3D fast spin echo (FSE) T₂‐weighted imaging method with uniform water and fat separation in a single acquisition, amenable to high‐quality multiplanar reformations.

Materials and Methods:

The Iterative Decomposition of water and fat with Echo Asymmetry and Least squares estimation (IDEAL) method was integrated with modulated refocusing flip angle 3D‐FSE. Echoes required for IDEAL processing were acquired by shifting the readout gradient with respect to the Carr‐Purcell‐Meiboom‐Gill echo. To reduce the scan time, an alternative data acquisition using two gradient echoes per repetition was implemented. Using the latter approach, a total of four gradient echoes were acquired in two repetitions and used in the modified IDEAL reconstruction.

Results:

3D‐FSE T₂‐weighted images with uniform water–fat separation were successfully acquired in various anatomies including breast, abdomen, knee, and ankle in clinically feasible scan times, ranging from 5:30–8:30 minutes. Using water‐only and fat‐only images, in‐phase and out‐of‐phase images were reconstructed.

Conclusion:

3D‐FSE‐IDEAL provides volumetric T₂‐weighted images with uniform water and fat separation in a single acquisition. High‐resolution images with multiple contrasts can be reformatted to any orientation from a single acquisition. This could potentially replace 2D‐FSE acquisitions with and without fat suppression and in multiple planes, thus improving overall imaging efficiency. J. Magn. Reson. Imaging 2010;32:745–751. © 2010 Wiley‐Liss, Inc.     

Phase‐contrast velocimetry with simultaneous fat/water separation

Phase‐contrast MRI can provide high‐resolution angiographic velocity images, especially in conjunction with non‐Cartesian k‐space sampling. However, acquisitions can be sensitive to errors from artifacts from main magnetic field inhomogeneities and chemical shift from fat. Particularly in body imaging, fat content can cause degraded image quality, create errors in the velocity measurements, and prevent the use of self‐calibrated amplitude of static field heterogeneity corrections. To reduce the influence of fat and facilitate self‐calibrated amplitude of static field heterogeneity corrections, a combination of chemical shift imaging with phase‐contrast velocimetry with nonlinear least‐squares estimation of velocity, fat, and water signals is proposed. A chemical shift and first‐moment symmetric dual‐echo sequence is proposed to minimize the scan time penalty, and initial investigations are performed in phantoms and volunteers that show reduced influence from fat in velocity images. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Fast three‐dimensional dual echo dixon technique improves fat suppression in breast MRI

Purpose:

To compare qualitative and quantitative measures of the contrast‐enhanced dual‐echo Dixon technique with the commonly used standard three‐dimensional (3D) gradient echo (spectrally selective fat suppression) technique (SS‐FS) in breast MRI exams (bMRI).

Materials and Methods:

A total of 19 women, with prescheduled bMRI exam, were recruited to our study between 2006 and 2008. Dixon and standard SS‐SF techniques were used on both breasts of each patient. Image quality was rated in five categories: fat suppression quality, fat suppression uniformity, lesion margin clarity, lesion visibility, and axillary visibility. For quantitative assessment, we calculated the signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) of lesion to breast, SNR efficiency, and CNR efficiency.

Results:

Of 19 patients evaluated, 13 had a primary breast malignancy and 6 had benign lesions or negative exams. Dixon images were rated higher in four of five qualitative categories (P < 0.0001) and required a shorter scan time. Dixon images yielded significantly higher SNR (43.8) and CNR (40.1) values than did 3DGRE images (SNR = 34.8, CNR = 25.3; P < 0.05). SNR efficiency (36.30) and CNR efficiency (33.79) values for Dixon images were also higher than were 3DGRE images (SNR efficiency =25.7, CNR efficiency = 19.1; P < 0.05).

Conclusion:

Dixon images were superior to the standard SS‐SF images in both qualitative and quantitative assessment of 19 bMRI exams. The Dixon technique could replace standard SS‐SF technique in bMRI exam, after our findings have been confirmed in future studies with a larger sample size. J. Magn. Reson. Imaging 2010;31:889–894. ©2010 Wiley‐Liss, Inc.