Abstract
Purpose
MRI proton density fat fraction (PDFF) can be calculated using magnitude (MRI-M) or complex (MRI-C) MRI data. The purpose of this study was to identify, assess, and compare the accuracy of common PDFF thresholds for MRI-M and MRI-C for assessing hepatic steatosis in patients with obesity, using histology as reference.
Methods
This two-center prospective study included patients undergoing MRI-C- and MRI-M-PDFF estimations within 3 days before weight loss surgery. Liver biopsy was performed, and histology-determined steatosis grades were used as reference standard. Using receiver operating characteristics (ROC) analysis on data pooled from both methods, single common thresholds for diagnosing and differentiating none or mild (0–1) from moderate to severe steatosis (2–3) were selected as the ones achieving the highest sensitivity while providing at least 90% specificity. Selection methods were cross-validated. Performances were compared using McNemar’s tests.
Results
Of 81 included patients, 54 (67%) had steatosis. The common PDFF threshold for diagnosing steatosis was 5.4%, which provided a cross-validated 0.88 (95% CI 0.77–0.95) sensitivity and 0.92 (0.75–0.99) specificity for MRI-M and 0.87 sensitivity (0.75–0.94) with 0.81 (0.61–0.93) specificity for MRI-C. The common PDFF threshold to differentiate steatosis grades 0–1 from 2 to 3 was 14.7%, which provided cross-validated 0.86 (95% CI 0.59–0.98) sensitivity and 0.95 (0.87–0.99) specificity for MRI-M and 0.93 sensitivity (0.68–0.99) with 0.97(0.89–0.99) specificity for MRI-C.
Conclusion
If independently validated, diagnostic thresholds of 5.4% and 14.7% could be adopted for both techniques for detecting and differentiating none to mild from moderate to severe steatosis, respectively, with high diagnostic accuracy.
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Abbreviations
- CSE-MRI:
-
Chemical shift-encoded-MRI
- MRI-M:
-
Magnitude-based data MRI
- MRI-C:
-
Complex-based data MRI
- PDFF:
-
Proton density fat fraction
- WLS:
-
Weight loss surgery
- NAFLD:
-
Non-alcoholic fatty liver disease
References
Younossi Z, Anstee QM, Marietti M, Hardy T, Henry L, Eslam M, George J, Bugianesi E. Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention. Nature reviews Gastroenterology & hepatology. 2018 Jan;15(1):11
Yokoo T, Serai SD, Pirasteh A, Bashir MR, Hamilton G, Hernando D, Hu HH, Hetterich H, Kühn JP, Kukuk GM, Loomba R. Linearity, bias, and precision of hepatic proton density fat fraction measurements by using MR imaging: a meta-analysis. Radiology. 2017 Sep 11;286(2):486-98.
[Withheld during submission for blinding purposes].
Bydder M, Yokoo T, Hamilton G, Middleton MS, Chavez AD, Schwimmer JB, Lavine JE, Sirlin CB. Relaxation effects in the quantification of fat using gradient echo imaging. Magnetic resonance imaging. 2008 Apr 1;26(3):347-59
Liu CY, McKenzie CA, Yu H, Brittain JH, Reeder SB. Fat quantification with IDEAL gradient echo imaging: correction of bias from T1 and noise. Magnetic Resonance in Medicine: An Official Journal of the International Society for Magnetic Resonance in Medicine. 2007 Aug;58(2):354-64.
Yu H, McKenzie CA, Shimakawa A, Vu AT, Brau AC, Beatty PJ, Pineda AR, Brittain JH, Reeder SB. Multiecho reconstruction for simultaneous water-fat decomposition and T2* estimation. Journal of Magnetic Resonance Imaging: An Official Journal of the International Society for Magnetic Resonance in Medicine. 2007 Oct;26(4):1153-61.
Yu H, Shimakawa A, McKenzie CA, Brodsky E, Brittain JH, Reeder SB. Multiecho water-fat separation and simultaneous R estimation with multifrequency fat spectrum modeling. Magnetic Resonance in Medicine: An Official Journal of the International Society for Magnetic Resonance in Medicine. 2008 Nov;60(5):1122-34.
Haufe WM, Wolfson T, Hooker CA, Hooker JC, Covarrubias Y, Schlein AN, Hamilton G, Middleton MS, Angeles JE, Hernando D, Reeder SB. Accuracy of PDFF estimation by magnitude‐based and complex‐based MRI in children with MR spectroscopy as a reference. Journal of Magnetic Resonance Imaging. 2017 Dec;46(6):1641-7.
Yu H, Shimakawa A, Hines CD, McKenzie CA, Hamilton G, Sirlin CB, Brittain JH, Reeder SB. Combination of complex‐based and magnitude‐based multiecho water‐fat separation for accurate quantification of fat‐fraction. Magnetic resonance in medicine. 2011 Jul;66(1):199-206.
Hernando D, Hines CD, Yu H, Reeder SB. Addressing phase errors in fat‐water imaging using a mixed magnitude/complex fitting method. Magnetic resonance in medicine. 2012 Mar;67(3):638-44.
Tang A, Tan J, Sun M, Hamilton G, Bydder M, Wolfson T, Gamst AC, Middleton M, Brunt EM, Loomba R, Lavine JE. Nonalcoholic fatty liver disease: MR imaging of liver proton density fat fraction to assess hepatic steatosis. Radiology. 2013 May;267(2):422-31
Tang A, Desai A, Hamilton G, Wolfson T, Gamst A, Lam J, Clark L, Hooker J, Chavez T, Ang BD, Middleton MS. Accuracy of MR imaging–estimated proton density fat fraction for classification of dichotomized histologic steatosis grades in nonalcoholic fatty liver disease. Radiology. 2014 Sep 22;274(2):416-25
Heba ER, Desai A, Zand KA, Hamilton G, Wolfson T, Schlein AN, Gamst A, Loomba R, Sirlin CB, Middleton MS. Accuracy and the effect of possible subject-based confounders of magnitude-based MRI for estimating hepatic proton density fat fraction in adults, using MR spectroscopy as reference. Journal of Magnetic Resonance Imaging. 2016 Feb;43(2):398-406.
Zand KA, Shah A, Heba E, Wolfson T, Hamilton G, Lam J, Chen J, Hooker JC, Gamst AC, Middleton MS, Schwimmer JB. Accuracy of multiecho magnitude-based MRI (M-MRI) for estimation of hepatic proton density fat fraction (PDFF) in children. Journal of Magnetic Resonance Imaging. 2015 Nov;42(5):1223-32.
Joshi M, Dillman JR, Singh K, Serai SD, Towbin AJ, Xanthakos S, Zhang B, Su W, Trout AT. Quantitative MRI of fatty liver disease in a large pediatric cohort: correlation between liver fat fraction, stiffness, volume, and patient-specific factors. Abdominal Radiology. 2018 May 1;43(5):1168-79.
Armstrong T, Ly KV, Murthy S, Ghahremani S, Kim GH, Calkins KL, Wu HH. Free-breathing quantification of hepatic fat in healthy children and children with nonalcoholic fatty liver disease using a multi-echo 3-D stack-of-radial MRI technique. Pediatric radiology. 2018 May 4:1-3.
Middleton MS, Heba ER, Hooker CA, Bashir MR, Fowler KJ, Sandrasegaran K, Brunt EM, Kleiner DE, Doo E, Van Natta ML, Lavine JE. Agreement between magnetic resonance imaging proton density fat fraction measurements and pathologist-assigned steatosis grades of liver biopsies from adults with nonalcoholic steatohepatitis. Gastroenterology. 2017 Sep 1;153(3):753-61.
França M, Alberich-Bayarri A, Martí-Bonmatí L, Oliveira P, Costa FE, Porto G, Vizcaíno JR, Gonzalez JS, Ribeiro E, Oliveira J, Miranda HP. Accurate simultaneous quantification of liver steatosis and iron overload in diffuse liver diseases with MRI. Abdominal Radiology. 2017 May 1;42(5):1434-43
Reeder, Scott B., Houchun H. Hu, and Claude B. Sirlin. “Proton density fat-fraction: a standardized MR-based biomarker of tissue fat concentration.” Journal of magnetic resonance imaging 36.5 (2012): 1011-1014.
Artz NS, Haufe WM, Hooker CA, Hamilton G, Wolfson T, Campos GM, Gamst AC, Schwimmer JB, Sirlin CB, Reeder SB. Reproducibility of MR-based liver fat quantification across field strength: Same-day comparison between 1.5 T and 3T in obese subjects. Journal of Magnetic Resonance Imaging. 2015 Sep;42(3):811-7
Kang BK, Yu ES, Lee SS, Lee Y, Kim N, Sirlin CB, Cho EY, Yeom SK, Byun JH, Park SH, Lee MG. Hepatic fat quantification: a prospective comparison of magnetic resonance spectroscopy and analysis methods for chemical-shift gradient echo magnetic resonance imaging with histologic assessment as the reference standard. Investigative radiology. 2012 Jun 1;47(6):368-75.
Idilman IS, Aniktar H, Idilman R, Kabacam G, Savas B, Elhan A, Celik A, Bahar K, Karcaaltincaba M. Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy. Radiology. 2013 Jun;267(3):767-75.
Kühn JP, Hernando D, Muñoz del Rio A, et al. Effect of multipeak spectral modeling of fat for liver iron and fat quantification: correlation of biopsy with MR imaging results. Radiology. 2012;265(1):133–142
Imajo K, Kessoku T, Honda Y, Tomeno W, Ogawa Y, Mawatari H, Fujita K, Yoneda M, Taguri M, Hyogo H, Sumida Y. Magnetic resonance imaging more accurately classifies steatosis and fibrosis in patients with nonalcoholic fatty liver disease than transient elastography. Gastroenterology. 2016 Mar 1;150(3):626-37
https://www.cdc.gov/obesity/adult/defining.html accessed in December 15, 2018
Mangus RS, Kubal CA, Fridell JA, Pena JM, Frost EM, Joseph Tector A. Alcohol abuse in deceased liver donors: impact on post-transplant outcomes. Liver International. 2015 Jan;35(1):171-5.
Kleiner DE, Brunt EM, Natta MV, et al. Design and Validation of a Histological Scoring System for Nonalcoholic Fatty Liver Disease. Hepatology. 2005;41(6):1313–21
Kang GH, Cruite I, Shiehmorteza M, Wolfson T, Gamst AC, Hamilton G, Bydder M, Middleton MS, Sirlin CB. Reproducibility of MRI-determined proton density fat fraction across two different MR scanner platforms. Journal of magnetic resonance imaging. 2011 Oct 1;34(4):928-34.
Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, Koteish A, Brancati FL, Clark JM. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988–1994. American journal of epidemiology. 2013 May 23;178(1):38-45.
Qureshi K, Abrams GA. Prevalence of biopsy-proven non-alcoholic fatty liver disease in severely obese subjects without metabolic syndrome. Clinical obesity. 2016 Apr;6(2):117-23.
Permutt Z, Le TA, Peterson MR, Seki E, Brenner DA, Sirlin C, Loomba R. Correlation between liver histology and novel magnetic resonance imaging in adult patients with non-alcoholic fatty liver disease–MRI accurately quantifies hepatic steatosis in NAFLD. Alimentary pharmacology & therapeutics. 2012 Jul 1;36(1):22-9.
Chalasani N, Wilson L, Kleiner DE, Cummings OW, Brunt EM, Ünalp A, NASH Clinical Research Network. Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease. Journal of hepatology. 2008 May 1;48(5):829-34.
de Graaf EL, Kench J, Dilworth P, Shackel NA, Strasser SI, Joseph D, Pleass H, Crawford M, McCaughan GW, Verran DJ. Grade of deceased donor liver macrovesicular steatosis impacts graft and recipient outcomes more than the Donor Risk Index. Journal of gastroenterology and hepatology. 2012 Mar;27(3):540-6.
Szczepaniak LS, Nurenberg P, Leonard D, Browning JD, Reingold JS, Grundy S, Hobbs HH, Dobbins RL. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. American Journal of Physiology-Endocrinology and Metabolism. 2005 Feb;288(2):E462-8
Hernando D, Liang ZP, Kellman P. Chemical shift–based water/fat separation: a comparison of signal models. Magnetic resonance in medicine. 2010 Sep;64(3):811-22.
Horng, Debra E., et al. “Comparison of R2* correction methods for accurate fat quantification in fatty liver.” Journal of Magnetic Resonance Imaging 37.2 (2013): 414-422.
Nasr P, Forsgren MF, Ignatova S, Dahlström N, Cedersund G, Leinhard OD, Norén B, Ekstedt M, Lundberg P, Kechagias S. Using a 3% proton density fat fraction as a cut-off value increases sensitivity of detection of hepatic steatosis, based on results from histopathology analysis. Gastroenterology. 2017 Jul 1;153(1):53-5.
Schwimmer JB, Middleton MS, Behling C, Newton KP, Awai HI, Paiz MN, Lam J, Hooker JC, Hamilton G, Fontanesi J, Sirlin CB. Magnetic resonance imaging and liver histology as biomarkers of hepatic steatosis in children with nonalcoholic fatty liver disease. Hepatology. 2015 Jun 1;61(6):1887-95
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Cunha, G.M., Thai, T.T., Hamilton, G. et al. Accuracy of common proton density fat fraction thresholds for magnitude- and complex-based chemical shift-encoded MRI for assessing hepatic steatosis in patients with obesity. Abdom Radiol 45, 661–671 (2020). https://doi.org/10.1007/s00261-019-02350-3
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DOI: https://doi.org/10.1007/s00261-019-02350-3