Ultraschall Med 2019; 40(06): 722-733
DOI: 10.1055/a-0660-9465
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Ultrasonic Adaptive Sound Speed Estimation for the Diagnosis and Quantification of Hepatic Steatosis: A Pilot Study

Ultraschall-adaptive Schallgeschwindigkeitsschätzung für die Diagnose und Quantifizierung der Leber-Steatose: Eine Pilotstudie
Marco Dioguardi Burgio
1   Radiology, Hopital Beaujon, Clichy, France
4   Center for Research on Inflammation, U1149 Inserm – University Paris Diderot, Paris, France
,
Marion Imbault
2   Institut Langevin, ESPCI Paris, INSERM U979, PSL Research University, CNRS UMR 7587, Paris, France
,
Maxime Ronot
1   Radiology, Hopital Beaujon, Clichy, France
4   Center for Research on Inflammation, U1149 Inserm – University Paris Diderot, Paris, France
,
Alex Faccinetto
1   Radiology, Hopital Beaujon, Clichy, France
,
Bernard E. Van Beers
1   Radiology, Hopital Beaujon, Clichy, France
4   Center for Research on Inflammation, U1149 Inserm – University Paris Diderot, Paris, France
,
Pierre-Emmanuel Rautou
3   Hepatology, Hopital Beaujon, Clichy, France
4   Center for Research on Inflammation, U1149 Inserm – University Paris Diderot, Paris, France
,
Laurent Castera
3   Hepatology, Hopital Beaujon, Clichy, France
,
Jean-Luc Gennisson
2   Institut Langevin, ESPCI Paris, INSERM U979, PSL Research University, CNRS UMR 7587, Paris, France
,
Mickael Tanter
2   Institut Langevin, ESPCI Paris, INSERM U979, PSL Research University, CNRS UMR 7587, Paris, France
,
Valérie Vilgrain
1   Radiology, Hopital Beaujon, Clichy, France
4   Center for Research on Inflammation, U1149 Inserm – University Paris Diderot, Paris, France
› Author Affiliations
Further Information

Publication History

28 December 2017

08 July 2018

Publication Date:
05 November 2018 (online)

Abstract

Purpose To evaluate the ability of a new ultrasound (US) method based on sound speed estimation (SSE) with respect to the detection, quantification, and grading of hepatic steatosis using magnetic resonance (MR) proton density fat fraction (PDFF) as the reference standard and to calculate one US fat index based on the patient’s SSE.

Materials and Methods This study received local IRB approval. Written informed consent was obtained from patients. We consecutively included N = 50 patients as the training cohort and a further N = 50 as the validation cohort who underwent both SSE and abdominal MR. Hepatic steatosis was classified according to MR-PDFF cutoffs as: S0 ≤ 6.5 %, S1 6.5 to 16.5 %, S2 16.5 to 22 %, S3 ≥ 22 %. Receiver operating curve analysis was performed to evaluate the diagnostic performance of SSE in the diagnosis of steatosis (S1–S3). Based on the optimal data fit derived from our study, we proposed a correspondence between the MR-PDFF and a US fat index. Coefficient of determination R2 was used to evaluate fit quality and was considered robust when R2 > 0.6.

Results The training and validation cohorts presented mean SSE values of 1.570 ± 0.026 and 1.568 ± 0.023 mm/µs for S0 and 1.521 ± 0.031 and 1.514 ± 0.019 mm/µs for S1–S3 (p < 0.01) patients, respectively. An SSE threshold of ≤ 1.537 mm/µs had a sensitivity of 80 % and a specificity of 85.7 % in the diagnosis of steatosis (S1-S3) in the training cohort. Robust correspondence between MR-PDFF and the US fat index was found both for the training (R2 = 0.73) and the validation cohort (R2 = 0.76).

Conclusion SSE can be used to detect, quantify and grade liver steatosis and to calculate a US fat index.

Zusammenfassung

Ziel Beurteilung der Leistungsfähigkeit einer innovativen Ultraschall-(US)-Methode auf Grundlage der Schallgeschwindigkeitsschätzung („sound speed estimation“ SSE) für den Nachweis, die Quantifizierung und Einstufung der Lebersteatose mit Magnetresonanz-(MR)-Protonendichtefettfraktion (PDFF) als Referenzstandard und die Berechnung eines US-Fettindex basierend auf der SSE des Patienten.

Material und Methoden Diese Studie erhielt eine lokale IRB-Zulassung. Eine schriftliche Einverständniserklärung der Patienten lag vor. Fortlaufend wurden N = 50 Patienten als Trainingskohorte und weitere N = 50 als Validierungskohorte eingeschlossen, bei denen sowohl eine SSE als auch eine abdominale MR durchgeführt wurde. Die hepatische Steatose wurde gemäß der MR-PDFF-Grenzwerte wie folgt klassifiziert: S0: ≤ 6,5 %, S1: 6,5 bis 16,5 %, S2: 16,5 bis 22 %, S3: ≥ 22%. Eine ROC-(„receiver operating curve“)-Analyse wurde durchgeführt, um die Leistung der SSE bei der Diagnose einer Steatose (S1–S3) zu ermitteln. Basierend auf der optimalen Datenanpassung, die aus unserer Studie abgeleitet wurde, schlugen wir eine Analogie zwischen MR-PDFF und einem US-Fettindex vor. Der Koeffizient der Bestimmung R2 wurde verwendet, um die Qualität der Anpassung zu bewerten und wurde als robust angesehen, wenn R2 > 0,6 betrug.

Ergebnisse Die Trainingskohorten zeigten mittlere SSE-Werte von 1,570 ± 0,026 für S0 und 1,521 ± 0,031 mm/μs für S1–S3-Patienten, während die Validierungskohorten für S0-Patienten 1,568 ± 0,023 und für S1–S3 1,514 ± 0,019 mm/μs aufwiesen (p < 0,01). Ein SSE-Grenzwert von ≤ 1,537 mm/μs hatte in der Trainingskohorte eine Sensitivität von 80 % und eine Spezifität von 85,7 % für die Diagnose der Steatose (S1–S3). Eine robuste Übereinstimmung zwischen MR-PDFF und dem US-Fettindex wurde sowohl für die Trainings- (R2 = 0,73) als auch für die Validierungskohorte (R2 = 0,76) ermittelt.

Schlussfolgerung SSE kann eingesetzt werden, um eine Lebersteatose zu detektieren, zu quantifizieren und zu einzustufen und um einen US-Fettindex zu berechnen.

 
  • References

  • 1 EASL-EASD-EASO. Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. Journal of hepatology 2016; 64: 1388-1402
  • 2 Browning JD, Szczepaniak LS, Dobbins R. et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004; 40: 1387-1395
  • 3 Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Alimentary pharmacology & therapeutics 2011; 34: 274-285
  • 4 Younossi ZM, Koenig AB, Abdelatif D. et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology 2016; 64: 73-84
  • 5 Ballestri S, Zona S, Targher G. et al. Nonalcoholic fatty liver disease is associated with an almost twofold increased risk of incident type 2 diabetes and metabolic syndrome. Evidence from a systematic review and meta-analysis. Journal of gastroenterology and hepatology 2016; 31: 936-944
  • 6 Targher G, Byrne CD, Lonardo A. et al. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: A meta-analysis. Journal of hepatology 2016; 65: 589-600
  • 7 Ekstedt M, Franzen LE, Mathiesen UL. et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology 2006; 44: 865-873
  • 8 Fishbein M, Castro F, Cheruku S. et al. Hepatic MRI for fat quantitation: its relationship to fat morphology, diagnosis, and ultrasound. Journal of clinical gastroenterology 2005; 39: 619-625
  • 9 Stern C, Castera L. Non-invasive diagnosis of hepatic steatosis. Hepatology international 2017; 11: 70-78
  • 10 Bril F, Ortiz-Lopez C, Lomonaco R. et al. Clinical value of liver ultrasound for the diagnosis of nonalcoholic fatty liver disease in overweight and obese patients. Liver international: official journal of the International Association for the Study of the Liver 2015; 35: 2139-2146
  • 11 Ballestri S, Nascimbeni F, Baldelli E. et al. Ultrasonographic fatty liver indicator detects mild steatosis and correlates with metabolic/histological parameters in various liver diseases. Metabolism: clinical and experimental 2017; 72: 57-65
  • 12 Dasarathy S, Dasarathy J, Khiyami A. et al. Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. Journal of hepatology 2009; 51: 1061-1067
  • 13 Bohte AE, van Werven JR, Bipat S. et al. The diagnostic accuracy of US, CT, MRI and 1H-MRS for the evaluation of hepatic steatosis compared with liver biopsy: a meta-analysis. European radiology 2011; 21: 87-97
  • 14 Ryan CK, Johnson LA, Germin BI. et al. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver transplantation: official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society 2002; 8: 1114-1122
  • 15 Strauss S, Gavish E, Gottlieb P. et al. Interobserver and intraobserver variability in the sonographic assessment of fatty liver. American journal of roentgenology 2007; 189: W320-W323
  • 16 Marshall RH, Eissa M, Bluth EI. et al. Hepatorenal index as an accurate, simple, and effective tool in screening for steatosis. American journal of roentgenology 2012; 199: 997-1002
  • 17 Hamaguchi M, Kojima T, Itoh Y. et al. The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation. The American journal of gastroenterology 2007; 102: 2708-2715
  • 18 Ballestri S, Lonardo A, Romagnoli D. et al. Ultrasonographic fatty liver indicator, a novel score which rules out NASH and is correlated with metabolic parameters in NAFLD. Liver international: official journal of the International Association for the Study of the Liver 2012; 32: 1242-1252
  • 19 Kwon HJ, Kim KW, Lee SJ. et al. Value of the ultrasound attenuation index for noninvasive quantitative estimation of hepatic steatosis. Journal of ultrasound in medicine: official journal of the American Institute of Ultrasound in Medicine 2013; 32: 229-235
  • 20 Son JY, Lee JY, Yi NJ. et al. Hepatic Steatosis: Assessment with Acoustic Structure Quantification of US Imaging. Radiology 2016; 278: 257-264
  • 21 Sasso M, Beaugrand M, de Ledinghen V. et al. Controlled attenuation parameter (CAP): a novel VCTE guided ultrasonic attenuation measurement for the evaluation of hepatic steatosis: preliminary study and validation in a cohort of patients with chronic liver disease from various causes. Ultrasound in medicine & biology 2010; 36: 1825-1835
  • 22 Karlas T, Petroff D, Sasso M. et al. Individual patient data meta-analysis of controlled attenuation parameter (CAP) technology for assessing steatosis. Journal of hepatology 2017; 66: 1022-1030
  • 23 Shi KQ, Tang JZ, Zhu XL. et al. Controlled attenuation parameter for the detection of steatosis severity in chronic liver disease: a meta-analysis of diagnostic accuracy. Journal of gastroenterology and hepatology 2014; 29: 1149-1158
  • 24 Imbault M, Faccinetto A, Osmanski BF. et al. Robust sound speed estimation for ultrasound-based hepatic steatosis assessment. Physics in medicine and biology 2017; 62: 3582-3598
  • 25 Tang A, Desai A, Hamilton G. et al. Accuracy of MR imaging-estimated proton density fat fraction for classification of dichotomized histologic steatosis grades in nonalcoholic fatty liver disease. Radiology 2015; 274: 416-425
  • 26 Idilman IS, Aniktar H, Idilman R. et al. Hepatic steatosis: quantification by proton density fat fraction with MR imaging versus liver biopsy. Radiology 2013; 267: 767-775
  • 27 Duck FA. Chapter 4 – Acoustic Properties of Tissue at Ultrasonic Frequencies. In: Physical Properties of Tissues. London: cademic Press; 1990: 73-135
  • 28 Ratziu V, Charlotte F, Heurtier A. et al. Sampling variability of liver biopsy in nonalcoholic fatty liver disease. Gastroenterology 2005; 128: 1898-1906
  • 29 Lee DH, Lee JY, Lee KB. et al. Evaluation of Hepatic Steatosis by Using Acoustic Structure Quantification US in a Rat Model: Comparison with Pathologic Examination and MR Spectroscopy. Radiology 2017; DOI: 10.1148/radiol.2017161923: 161923.
  • 30 Lin SC, Heba E, Wolfson T. et al. Noninvasive Diagnosis of Nonalcoholic Fatty Liver Disease and Quantification of Liver Fat Using a New Quantitative Ultrasound Technique. Clinical gastroenterology and hepatology: the official clinical practice journal of the American Gastroenterological Association 2015; 13: 1337-1345 e1336
  • 31 de Ledinghen V, Vergniol J, Capdepont M. et al. Controlled attenuation parameter (CAP) for the diagnosis of steatosis: a prospective study of 5323 examinations. Journal of hepatology 2014; 60: 1026-1031
  • 32 Tchoukalova YD, Koutsari C, Karpyak MV. et al. Subcutaneous adipocyte size and body fat distribution. The American journal of clinical nutrition 2008; 87: 56-63