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ABSTRACT: A theoretical triglyceride model was developed for in vivo human liver fat (1) H MRS characterization, using the number of double bonds (-CH=CH-), number of methylene-interrupted double bonds (-CH=CH-CH(2)-CH=CH-) and average fatty acid chain length. Five 3 T, single-voxel, stimulated echo acquisition mode spectra (STEAM) were acquired consecutively at progressively longer TEs in a fat-water emulsion phantom and in 121 human subjects with known or suspected nonalcoholic fatty liver disease. T(2)-corrected peak areas were calculated. Phantom data were used to validate the model. Human data were used in the model to determine the complete liver fat spectrum. In the fat-water emulsion phantom, the spectrum predicted by the model (based on known fatty acid chain distribution) agreed closely with spectroscopic measurement. In human subjects, areas of CH(2) peaks at 2.1 and 1.3 ppm were linearly correlated (slope, 0.172; r = 0.991), as were the 0.9 ppm CH(3) and 1.3 ppm CH(2) peaks (slope, 0.125; r = 0.989). The 2.75 ppm CH(2) peak represented 0.6% of the total fat signal in high-liver-fat subjects. These values predict that 8.6% of the total fat signal overlies the water peak. The triglyceride model can characterize human liver fat spectra. This allows more accurate determination of liver fat fraction from MRI and MRS.
NMR in Biomedicine 08/2011; 24(7):784-90. · 3.21 Impact Factor
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Takeshi Yokoo,
Masoud Shiehmorteza,
Gavin Hamilton,
Tanya Wolfson,
Michael E Schroeder,
Michael S Middleton,
Mark Bydder,
Anthony C Gamst,
Yuko Kono,
Alexander Kuo,
Heather M Patton,
Santiago Horgan,
Joel E Lavine,
Jeffrey B Schwimmer,
Claude B Sirlin
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ABSTRACT: To compare the accuracy of several magnetic resonance (MR) imaging-based methods for hepatic proton-density fat fraction (FF) estimation at 3.0 T, with spectroscopy as the reference technique.
This prospective study was institutional review board approved and HIPAA compliant. Informed consent was obtained. One hundred sixty-three subjects (39 with known hepatic steatosis, 110 with steatosis risk factors, 14 without risk factors) underwent proton MR spectroscopy and non-T1-weighted gradient-echo MR imaging of the liver. At spectroscopy, the reference FF was determined from frequency-selective measurements of fat and water proton densities. At imaging, FF was calculated by using two-, three-, or six-echo methods, with single-frequency and multifrequency fat signal modeling. The three- and six-echo methods corrected for T2*; the two-echo methods did not. For each imaging method, the fat estimation accuracy was assessed by using linear regression between the imaging FF and spectroscopic FF. Binary classification accuracy of imaging was assessed at four reference spectroscopic thresholds (0.04, 0.06, 0.08, and 0.10 FF).
Regression intercept of two-, three-, and six-echo methods were -0.0211, 0.0087, and -0.0062 (P <.001 for all three) without multifrequency modeling and -0.0237 (P <.001), 0.0022, and -0.0007 with multifrequency modeling, respectively. Regression slope of two-, three-, and six-echo methods were 0.8522, 0.8528, and 0.7544 (P <.001 for all three) without multifrequency modeling and 0.9994, 0.9775, and 0.9821 with multifrequency modeling, respectively. Significant deviation of intercept and slope from 0 and 1, respectively, indicated systematic error. Classification accuracy was 82.2%-90.1%, 93.9%-96.3%, and 83.4%-89.6% for two-, three-, and six-echo methods without multifrequency modeling and 88.3%-92.0%, 95.1%-96.3%, and 94.5%-96.3% with multifrequency modeling, respectively, depending on the FF threshold. T2*-corrected (three- and six-echo) multifrequency imaging methods had the overall highest FF estimation and classification accuracy. Among methods without multifrequency modeling, the T2-corrected three-echo method had the highest accuracy.
Non-T1-weighted MR imaging with T2 correction and multifrequency modeling helps accurately estimate hepatic proton-density FF at 3.0 T.
Radiology 03/2011; 258(3):749-59. · 5.73 Impact Factor
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ABSTRACT: An algorithm is described for use in chemical shift-based water-fat separation to constrain the phase of both species to be equal at an echo time of zero. This constraint is physically reasonable since the initial phase should be a property of the excitation pulse and receiver coil only. The advantages of phase constrained water-fat separation, namely, improved noise performance and/or reduced data requirements (fewer echos), are demonstrated in simulations and experiments.
Magnetic Resonance Imaging 02/2011; 29(2):216-21. · 1.99 Impact Factor
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ABSTRACT: This study assesses the stability of magnetic resonance liver fat measurements against changes in T2* due to the presence of iron, which is a confound for accurate quantification. The liver T2* was experimentally shortened by intravenous infusion of a super paramagnetic iron oxide contrast agent. Low flip angle multiecho gradient echo sequences were performed before, during and after infusion. The liver fat fraction (FF) was calculated in co-localized regions-of-interest using T2* models that assumed no decay, monoexponential decay and biexponential decay. Results show that, when T2* was neglected, there was a strong underestimation of FF and with monoexponential decay there was a weak overestimation of FF. Curve-fitting using the biexponential decay was found to be problematic. The overestimation of FF may be due to remaining deficiencies in the model, although is unlikely to be important for clinical diagnosis of steatosis.
Magnetic Resonance Imaging 07/2010; 28(6):767-76. · 1.99 Impact Factor
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ABSTRACT: To compare PRESS and STEAM MR spectroscopy for assessment of liver fat in human subjects.
Single-voxel (20 x 20 x 20 mm) PRESS and STEAM spectra were obtained at 1.5T in 49 human subjects with known or suspected fatty liver disease. PRESS and STEAM sequences were obtained with fixed TR (1500 msec) and different TE (five PRESS spectra between TE 30-70 msec, five STEAM spectra between TE 20-60 msec). Spectra were quantified and T2 and T2-corrected peak area were calculated by different techniques. The values were compared for PRESS and STEAM.
Water T2 values from PRESS and STEAM were not significantly different (P = 0.33). Fat peak T2s were 25%-50% shorter on PRESS than on STEAM (P < 0.02 for all comparisons) and there was no correlation between T2s of individual peaks. PRESS systematically overestimated the relative fat peak areas (by 7%-263%) compared to STEAM (P < 0.005 for all comparisons). The peak area given by PRESS was more dependent on the T2-correction technique than STEAM.
Measured liver fat depends on the MRS sequence used. Compared to STEAM, PRESS underestimates T2 values of fat, overestimates fat fraction, and provides a less consistent fat fraction estimate, probably due to J coupling effects.
Journal of Magnetic Resonance Imaging 06/2009; 30(1):145-52. · 2.70 Impact Factor
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Takeshi Yokoo,
Mark Bydder,
Gavin Hamilton,
Michael S Middleton,
Anthony C Gamst,
Tanya Wolfson,
Tarek Hassanein,
Heather M Patton,
Joel E Lavine,
Jeffrey B Schwimmer,
Claude B Sirlin
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ABSTRACT: To assess the accuracy of four fat quantification methods at low-flip-angle multiecho gradient-recalled-echo (GRE) magnetic resonance (MR) imaging in nonalcoholic fatty liver disease (NAFLD) by using MR spectroscopy as the reference standard.
In this institutional review board-approved, HIPAA-compliant prospective study, 110 subjects (29 with biopsy-confirmed NAFLD, 50 overweight and at risk for NAFLD, and 31 healthy volunteers) (mean age, 32.6 years +/- 15.6 [standard deviation]; range, 8-66 years) gave informed consent and underwent MR spectroscopy and GRE MR imaging of the liver. Spectroscopy involved a long repetition time (to suppress T1 effects) and multiple echo times (to estimate T2 effects); the reference fat fraction (FF) was calculated from T2-corrected fat and water spectral peak areas. Imaging involved a low flip angle (to suppress T1 effects) and multiple echo times (to estimate T2* effects); imaging FF was calculated by using four analysis methods of progressive complexity: dual echo, triple echo, multiecho, and multiinterference. All methods except dual echo corrected for T2* effects. The multiinterference method corrected for multiple spectral interference effects of fat. For each method, the accuracy for diagnosis of fatty liver, as defined with a spectroscopic threshold, was assessed by estimating sensitivity and specificity; fat-grading accuracy was assessed by comparing imaging and spectroscopic FF values by using linear regression.
Dual-echo, triple-echo, multiecho, and multiinterference methods had a sensitivity of 0.817, 0.967, 0.950, and 0.983 and a specificity of 1.000, 0.880, 1.000, and 0.880, respectively. On the basis of regression slope and intercept, the multiinterference (slope, 0.98; intercept, 0.91%) method had high fat-grading accuracy without statistically significant error (P > .05). Dual-echo (slope, 0.98; intercept, -2.90%), triple-echo (slope, 0.94; intercept, 1.42%), and multiecho (slope, 0.85; intercept, -0.15%) methods had statistically significant error (P < .05).
Relaxation- and interference-corrected fat quantification at low-flip-angle multiecho GRE MR imaging provides high diagnostic and fat-grading accuracy in NAFLD.
Radiology 02/2009; 251(1):67-76. · 5.73 Impact Factor
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Jeffrey B Schwimmer,
Manuel A Celedon,
Joel E Lavine,
Rany Salem,
Nzali Campbell,
Nicholas J Schork,
Masoud Shiehmorteza, Takeshi Yokoo,
Alyssa Chavez,
Michael S Middleton,
Claude B Sirlin
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ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the United States. The etiology is believed to be multifactorial with a substantial genetic component; however, the heritability of NAFLD is undetermined. Therefore, a familial aggregation study was performed to test the hypothesis that NAFLD is highly heritable.
Overweight children with biopsy-proven NAFLD and overweight children without NAFLD served as probands. Family members were studied, including the use of magnetic resonance imaging to quantify liver fat fraction. Fatty liver was defined as a liver fat fraction of 5% or higher. Etiologies for fatty liver other than NAFLD were excluded. Narrow-sense heritability estimates for fatty liver (dichotomous) and fat fraction (continuous) were calculated using variance components analysis adjusted for covariate effects.
Fatty liver was present in 17% of siblings and 37% of parents of overweight children without NAFLD. Fatty liver was significantly more common in siblings (59%) and parents (78%) of children with NAFLD. Liver fat fraction was correlated with body mass index, although the correlation was significantly stronger for families of children with NAFLD than those without NAFLD. Adjusted for age, sex, race, and body mass index, the heritability of fatty liver was 1.000 and of liver fat fraction was 0.386.
Family members of children with NAFLD should be considered at high risk for NAFLD. These data suggest that familial factors are a major determinant of whether an individual has NAFLD. Studies examining the complex relations between genes and environment in the development and progression of NAFLD are warranted.
Gastroenterology 01/2009; 136(5):1585-92. · 11.68 Impact Factor
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ABSTRACT: A method for making weighted linear combinations of the spectra acquired by a phased-array coil is described. Unlike most previous combination methods, no special reference points in the data are chosen to represent the coil weights. Instead, all the data points are used, which results in optimal signal-to-noise ratio more reliable estimation. The method uses singular value decomposition to identify the coil weights and extract the principal component of variation in the signal. Subsequent processing of the combined signal (e.g., Fourier transform, baseline correction, phasing) may proceed as per a single coil acquisition.
Magnetic Resonance Imaging 08/2008; 26(6):847-50. · 1.99 Impact Factor
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ABSTRACT: To assess the effects of intravenous gadolinium (Gd) and flip angle (FA) on liver fat quantification by opposed-phase (OP) and in-phase (IP) imaging.
Our Institutional Review Board (IRB) approved this Health Insurance Portability and Accountability Act (HIPAA)-compliant, retrospective, clinical study. We identified 79 patients in whom abdominal OP and IP gradient-echoes were obtained at 1.5T before and after Gd administration. All 79 patients were imaged at high FA (> or =70 degrees ); 57 were also imaged at low FA (< or =20 degrees ). Fat signal fraction (FSF) was calculated from pre- and post-Gd liver images for each subject and FA using the formula, FSF = (S(IP) - S(OP))/2S(IP), where S(IP) and S(OP) are the OP and IP signal intensities, respectively. The dataset pairs (pre-Gd vs. post-Gd; high-FA vs. low-FA) were compared using linear regression analysis.
Before Gd, FSF was significantly greater at high FA than at low FA, with regression parameters (slope/intercept) of 1.27*/0.02*, where * indicates P value <0.01. After Gd, FSF was similar at high and low FA (0.99/-0.00). Gd administration caused an FA-dependent reduction in FSF, larger at high FA (0.68*/-0.03*) than at low FA (0.94, -0.01*).
FSF by OP-IP imaging is highly dependent on FA before Gd, but this dependency is eliminated after administration of Gd. Gd appears to minimize the effect of T1-weighting and may improve the accuracy of liver fat quantification.
Journal of Magnetic Resonance Imaging 07/2008; 28(1):246-51. · 2.70 Impact Factor
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ABSTRACT: Quantification of fat has been investigated using images acquired from multiple gradient echoes. The evolution of the signal with echo time and flip angle was measured in phantoms of known fat and water composition and in 21 research subjects with fatty liver. Data were compared to different models of the signal equation, in which each model makes different assumptions about the T1 and/or T2* relaxation effects. A range of T1, T2*, fat fraction and number of echoes was investigated to cover situations of relevance to clinical imaging. Results indicate that quantification is most accurate at low flip angles (to minimize T1 effects) with a small number of echoes (to minimize spectral broadening effects). At short echo times, the spectral broadening effects manifest as a short apparent T2 for the fat component.
Magnetic Resonance Imaging 05/2008; 26(3):347-59. · 1.99 Impact Factor
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Takeshi Yokoo,
Won C Bae,
Gavin Hamilton,
Afshin Karimi,
James P Borgstede,
Brian C Bowen,
Claude B Sirlin,
Christine B Chung,
John V Crues,
William G Bradley,
Graeme M Bydder
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ABSTRACT: Weighting is the term most frequently used to describe magnetic resonance pulse sequences and the concept most commonly used to relate image contrast to differences in magnetic resonance tissue properties. It is generally used in a qualitative sense with the single tissue property thought to be most responsible for the contrast used to describe the weighting of the image as a whole. This article describes a quantitative approach for understanding the weighting of sequences and images, using filters and partial derivatives of signal with respect to logarithms of tissue property values. Univariate and multivariate models are described for several pulse sequences including methods for maximizing weighting and calculating both sequence and image weighting ratios. The approach provides insights into difficulties associated with qualitative use of the concept of weighting and a quantitative basis for assessing the signal, contrast, and weighting of commonly used sequences and images.
Journal of computer assisted tomography 34(3):317-31. · 1.38 Impact Factor
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ABSTRACT: Fatty liver disease is the most common cause of chronic liver disease in the United States. Noninvasive detection and quantification of fat is becoming more and more important clinically, due in large part to the growing prevalence of nonalcoholic fatty liver disease. Steatosis, the accumulation of fat-containing vacuoles within hepatocytes, is a key histologic feature of fatty liver disease. Liver biopsy, the current standard of reference for the assessment of steatosis, is invasive, has sampling errors, and is not appropriate in some settings. Several magnetic resonance (MR) imaging-based techniques--including chemical shift imaging, frequency-selective imaging, and MR spectroscopy--are currently in clinical use for the detection and quantification of fat-water admixtures, with each technique having important advantages, disadvantages, and limitations. These techniques permit the breakdown of the net MR signal into fat and water signal components, allowing the quantification of fat in liver tissue, and are increasingly being used in the diagnosis, treatment, and follow-up of fatty liver disease.
Radiographics 29(1):231-60. · 2.85 Impact Factor
