Comparison between dynamic gadoxetate-enhanced MRI and 99mTc-mebrofenin hepatobiliary scintigraphy with SPECT for quantitative assessment of liver function

F Rassam, T Zhang, K P Cieslak, C Lavini, J Stoker, R J Bennink, T M van Gulik, L J van Vliet, J H Runge, F M Vos, F Rassam, T Zhang, K P Cieslak, C Lavini, J Stoker, R J Bennink, T M van Gulik, L J van Vliet, J H Runge, F M Vos

Abstract

Objectives: To compare Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) with 99mTc-mebrofenin hepatobiliary scintigraphy (HBS) as quantitative liver function tests for the preoperative assessment of patients undergoing liver resection.

Methods: Patients undergoing liver surgery and preoperative assessment of future remnant liver (FRL) function using 99mTc-mebrofenin HBS were included. Patients underwent DHCE-MRI. Total liver uptake function was calculated for both modalities: mebrofenin uptake rate (MUR) and Ki respectively. The FRL was delineated with both SPECT-CT and MRI to calculate the functional share. Blood samples were taken to assess biochemical liver parameters.

Results: A total of 20 patients were included. The HBS-derived MUR and the DHCE-MRI-derived mean Ki correlated strongly for both total and FRL function (Pearson r = 0.70, p = 0.001 and r = 0.89, p < 0.001 respectively). There was a strong agreement between the functional share determined with both modalities (ICC = 0.944, 95% CI 0.863-0.978, n = 20). There was a significant negative correlation between liver aminotransferases and bilirubin for both MUR and Ki.

Conclusions: Assessment of liver function with DHCE-MRI is comparable with that of 99mTc-mebrofenin HBS and has the potential to be combined with diagnostic MRI imaging. This can therefore provide a one-stop-shop modality for the preoperative assessment of patients undergoing liver surgery.

Key points: • Quantitative assessment of liver function using hepatobiliary scintigraphy is performed in the preoperative assessment of patients undergoing liver surgery in order to prevent posthepatectomy liver failure. • Gd-EOB-DTPA dynamic hepatocyte-specific contrast-enhanced MRI (DHCE-MRI) is an emerging method to quantify liver function and can serve as a potential alternative to hepatobiliary scintigraphy. • Assessment of liver function with dynamic gadoxetate-enhanced MRI is comparable with that of hepatobiliary scintigraphy and has the potential to be combined with diagnostic MRI imaging.

Keywords: Gadolinium ethoxybenzyl DTPA; Liver function tests; Magnetic resonance imaging; Technetium Tc 99m mebrofenin.

Conflict of interest statement

The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article.

Figures

Fig. 1
Fig. 1
Hepatobiliary scintigraphy with series scintigram (a), ROI on summed images (b), and FRL delineation on SPECT/CT (c)
Fig. 2
Fig. 2
DHCE-MRI protocol
Fig. 3
Fig. 3
Signal intensity curve with semi-quantitative parameters
Fig. 4
Fig. 4
Pearson correlation between total liver function represented by the mebrofenin uptake rate (MUR; %/min) and the Gd-EOB-DTPA uptake rate (Ki; min−1)
Fig. 5
Fig. 5
Bland-Altman plot for the agreement between functional share (%) of the FRL measured with SPECT and MRI
Fig. 6
Fig. 6
Pearson correlation between future remnant liver function represented by the mebrofenin uptake rate (fMUR; %/min) and the Gd-EOB-DTPA uptake rate (fKi; min−1)

References

    1. Agrawal S, Belghiti J. Oncologic resection for malignant tumors of the liver. Ann Surg. 2011;253:656–665. doi: 10.1097/SLA.0b013e3181fc08ca.
    1. Jarnagin WR, Gonen M, Fong Y, et al. Improvement in perioperative outcome after hepatic resection: analysis of 1,803 consecutive cases over the past decade. Ann Surg. 2002;236:397–406. doi: 10.1097/00000658-200210000-00001.
    1. van den Broek MA, Olde Damink SW, Dejong CH, et al. Liver failure after partial hepatic resection: definition, pathophysiology, risk factors and treatment. Liver Int. 2008;28:767–780. doi: 10.1111/j.1478-3231.2008.01777.x.
    1. Belghiti J, Hiramatsu K, Benoist S, Massault PP, Sauvanet A, Farges O. Seven hundred forty-seven hepatectomies in the 1990s: an update to evaluate the actual risk of liver resection 11. No competing interests declared. J Am Coll Surg. 2000;191:38–46. doi: 10.1016/S1072-7515(00)00261-1.
    1. Laurent C, Sa Cunha A, Couderc P, Rullier E, Saric J. Influence of postoperative morbidity on long-term survival following liver resection for colorectal metastases. Br J Surg. 2003;90:1131–1136. doi: 10.1002/bjs.4202.
    1. Ghibellini G, Leslie EM, Pollack GM, Brouwer KL. Use of tc-99m mebrofenin as a clinical probe to assess altered hepatobiliary transport: integration of in vitro, pharmacokinetic modeling, and simulation studies. Pharm Res. 2008;25:1851–1860. doi: 10.1007/s11095-008-9597-0.
    1. Bennink RJ, Tulchinsky M, de Graaf W, Kadry Z, van Gulik TM. Liver function testing with nuclear medicine techniques is coming of age. Semin Nucl Med. 2012;42:124–137. doi: 10.1053/j.semnuclmed.2011.10.003.
    1. de Graaf W, Häusler S, Heger M, et al. Transporters involved in the hepatic uptake of (99m)Tc-mebrofenin and indocyanine green. J Hepatol. 2011;54:738–745. doi: 10.1016/j.jhep.2010.07.047.
    1. de Graaf W, van Lienden KP, Dinant S, et al. Assessment of future remnant liver function using hepatobiliary scintigraphy in patients undergoing major liver resection. J Gastrointest Surg. 2010;14:369–378. doi: 10.1007/s11605-009-1085-2.
    1. de Graaf W, van Lienden KP, van Gulik TM, Bennink RJ. (99m)Tc-mebrofenin hepatobiliary scintigraphy with SPECT for the assessment of hepatic function and liver functional volume before partial hepatectomy. J Nucl Med. 2010;51:229–236. doi: 10.2967/jnumed.109.069724.
    1. Cieslak KP, Bennink RJ, de Graaf W, et al. Measurement of liver function using hepatobiliary scintigraphy improves risk assessment in patients undergoing major liver resection. HPB (Oxford) 2016;18:773–780. doi: 10.1016/j.hpb.2016.06.006.
    1. Erdogan D, Heijnen BH, Bennink RJ, et al. Preoperative assessment of liver function: a comparison of 99mTc-mebrofenin scintigraphy with indocyanine green clearance test. Liver Int. 2004;24:117–123. doi: 10.1111/j.1478-3231.2004.00901.x.
    1. Dinant S, de Graaf W, Verwer BJ, et al. Risk assessment of posthepatectomy liver failure using hepatobiliary scintigraphy and CT volumetry. J Nucl Med. 2007;48:685–692. doi: 10.2967/jnumed.106.038430.
    1. Schuhmann-Giampieri G. Liver contrast media for magnetic resonance imaging interrelations between pharmacokinetics and imaging. Invest Radiol. 1993;28:753–761. doi: 10.1097/00004424-199308000-00018.
    1. Schmitz SA, Mühler A, Wagner S, Wolf KJ. Functional hepatobiliary imaging with gadolinium-EOB-DTPA. A comparison of magnetic resonance imaging and 153gadolinium-EOB-DTPA scintigraphy in rats. Invest Radiol. 1996;31:154–160. doi: 10.1097/00004424-199603000-00006.
    1. Kim T, Murakami T, Hasuike Y, et al. Experimental hepatic dysfunction: evaluation by MRI with Gd-EOB-DTPA. J Magn Reson Imaging. 1997;7:683–688. doi: 10.1002/jmri.1880070413.
    1. Shimizu J, Dono K, Gotoh M, et al. Evaluation of reginal liver function by gadolinium-EOB-DTPA enhanced MR imaging. Gastroenterology. 1998;114:A1342.
    1. Ryeom HK, Kim SH, Kim JY, et al. Quantitative evaluation of liver function with MRI using Gd-EOB-DTPA. Korean J Radiol. 2004;5:231–239. doi: 10.3348/kjr.2004.5.4.231.
    1. Tsuda N, Okada M, Murakami T. Potential of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) for differential diagnosis of nonalcoholic steatohepatitis and fatty liver in rats using magnetic resonance imaging. Invest Radiol. 2007;42:242–247. doi: 10.1097/01.rli.0000258058.44876.a5.
    1. Tsuda N, Okada M, Murakami T. New proposal for the staging of nonalcoholic steatohepatitis: evaluation of liver fibrosis on Gd-EOB-DTPA-enhanced MRI. Eur J Radiol. 2010;73:137–142. doi: 10.1016/j.ejrad.2008.09.036.
    1. Haimerl M, Fuhrmann I, Poelsterl S, et al. Gd-EOB-DTPA-enhanced T1 relaxometry for assessment of liver function determined by real-time (13)C-methacetin breath test. Eur Radiol. 2018;28:3591–3600. doi: 10.1007/s00330-018-5337-y.
    1. Asenbaum U, Kaczirek K, Ba-Ssalamah A et al (2018) Post-hepatectomy liver failure after major hepatic surgery: not only size matters. Eur Radiol. 10.1007/s00330-018-5487-y
    1. Niekel MC, Bipat S, Stoker J. Diagnostic imaging of colorectal liver metastases with CT, MR imaging, FDG PET, and/or FDG PET/CT: a meta-analysis of prospective studies including patients who have not previously undergone treatment. Radiology. 2010;257:674–684. doi: 10.1148/radiol.10100729.
    1. Liu X, Jiang H, Chen J, Zhou Y, Huang Z, Song B. Gadoxetic acid disodium-enhanced magnetic resonance imaging outperformed multidetector computed tomography in diagnosing small hepatocellular carcinoma: a meta-analysis. Liver Transpl. 2017;23:1505–1518. doi: 10.1002/lt.24867.
    1. Chung YE, Kim MJ, Kim YE, Park MS, Choi JY, Kim KW. Characterization of incidental liver lesions: comparison of multidetector CT versus Gd-EOB-DTPA-enhanced MR imaging. PLoS One. 2013;8:e66141. doi: 10.1371/journal.pone.0066141.
    1. Sourbron S, Sommer WH, Reiser MF, Zech CJ. Combined quantification of liver perfusion and function with dynamic gadoxetic acid-enhanced MR imaging. Radiology. 2012;263:874–883. doi: 10.1148/radiol.12110337.
    1. Forsgren MF, Dahlqvist Leinhard O, Dahlstrom N, Cedersund G, Lundberg P. Physiologically realistic and validated mathematical liver model reveals [corrected] hepatobiliary transfer rates for Gd-EOB-DTPA using human DCE-MRI data. PLoS One. 2014;9:e95700. doi: 10.1371/journal.pone.0095700.
    1. Nilsson H, Blomqvist L, Douglas L, et al. Gd-EOB-DTPA-enhanced MRI for the assessment of liver function and volume in liver cirrhosis. Br J Radiol. 2013;86:20120653. doi: 10.1259/bjr.20120653.
    1. Ekman M, Fjälling M, Friman S, Carlson S, Volkmann R. Liver uptake function measured by IODIDA clearance rate in liver transplant patients and healthy volunteers. Nucl Med Commun. 1996;17:235–242. doi: 10.1097/00006231-199603000-00011.
    1. Geisel D, Lüdemann L, Fröling V, et al. Imaging-based evaluation of liver function: comparison of (9)(9)mTc-mebrofenin hepatobiliary scintigraphy and Gd-EOB-DTPA-enhanced MRI. Eur Radiol. 2015;25:1384–1391. doi: 10.1007/s00330-014-3536-8.
    1. Leonhardt M, Keiser M, Oswald S, et al. Hepatic uptake of the magnetic resonance imaging contrast agent Gd-EOB-DTPA: role of human organic anion transporters. Drug Metab Dispos. 2010;38:1024–1028. doi: 10.1124/dmd.110.032862.
    1. Van Beers BE, Pastor CM, Hussain HK. Primovist, Eovist: what to expect? J Hepatol. 2012;57:421–429. doi: 10.1016/j.jhep.2012.01.031.
    1. Tajima T, Takao H, Akai H, et al. Relationship between liver function and liver signal intensity in hepatobiliary phase of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging. J Comput Assist Tomogr. 2010;34:362–366. doi: 10.1097/RCT.0b013e3181cd3304.
    1. Verloh N, Haimerl M, Rennert J, et al. Impact of liver cirrhosis on liver enhancement at Gd-EOB-DTPA enhanced MRI at 3 Tesla. Eur J Radiol. 2013;82:1710–1715. doi: 10.1016/j.ejrad.2013.05.033.
    1. Hamm B, Staks T, Mühler A, et al. Phase I clinical evaluation of Gd-EOB-DTPA as a hepatobiliary MR contrast agent: safety, pharmacokinetics, and MR imaging. Radiology. 1995;195:785–792. doi: 10.1148/radiology.195.3.7754011.
    1. Mühler A, Oude Elferink RPJ, Weinmann H-J. Complete elimination of the hepatobiliary mr contrast agent Gd-EOB-DTPA in hepatic dysfunction: an experimental study using transport-deficient, mutant rats. MAGMA. 1993;1:134–139. doi: 10.1007/BF01769415.
    1. Gschwend S, Ebert W, Schultze-Mosgau M, Breuer J. Pharmacokinetics and imaging properties of Gd-EOB-DTPA in patients with hepatic and renal impairment. Invest Radiol. 2011;46:556–566. doi: 10.1097/RLI.0b013e31821a218a.
    1. Nilsson H, Nordell A, Vargas R, Douglas L, Jonas E, Blomqvist L. Assessment of hepatic extraction fraction and input relative blood flow using dynamic hepatocyte-specific contrast-enhanced MRI. J Magn Reson Imaging. 2009;29:1323–1331. doi: 10.1002/jmri.21801.
    1. Ulloa JL, Stahl S, Yates J, et al. Assessment of gadoxetate DCE-MRI as a biomarker of hepatobiliary transporter inhibition. NMR Biomed. 2013;26:1258–1270. doi: 10.1002/nbm.2946.
    1. Truhn D, Kuhl CK, Ciritsis A, Barabasch A, Kraemer NA. A new model for MR evaluation of liver function with gadoxetic acid, including both uptake and excretion. Eur Radiol. 2019;29:383–391. doi: 10.1007/s00330-018-5500-5.
    1. Ning J, Yang Z, Xie S, Sun Y, Yuan C, Chen H. Hepatic function imaging using dynamic Gd-EOB-DTPA enhanced MRI and pharmacokinetic modeling. Magn Reson Med. 2017;78:1488–1495. doi: 10.1002/mrm.26520.
    1. Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973;60:646–649. doi: 10.1002/bjs.1800600817.
    1. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33:464–470. doi: 10.1053/jhep.2001.22172.
    1. Kukuk GM, Schaefer SG, Fimmers R, et al. Hepatobiliary magnetic resonance imaging in patients with liver disease: correlation of liver enhancement with biochemical liver function tests. Eur Radiol. 2014;24:2482–2490. doi: 10.1007/s00330-014-3291-x.
    1. Talakic E, Steiner J, Kalmar P, et al. Gd-EOB-DTPA enhanced MRI of the liver: correlation of relative hepatic enhancement, relative renal enhancement, and liver to kidneys enhancement ratio with serum hepatic enzyme levels and eGFR. Eur J Radiol. 2014;83:607–611. doi: 10.1016/j.ejrad.2013.12.010.
    1. Feng L, Axel L, Chandarana H, Block KT, Sodickson DK, Otazo R. XD-GRASP: golden-angle radial MRI with reconstruction of extra motion-state dimensions using compressed sensing. Magn Reson Med. 2016;75:775–788. doi: 10.1002/mrm.25665.
    1. Feng L, Grimm R, Block KT, et al. Golden-angle radial sparse parallel MRI: combination of compressed sensing, parallel imaging, and golden-angle radial sampling for fast and flexible dynamic volumetric MRI. Magn Reson Med. 2014;72:707–717. doi: 10.1002/mrm.24980.
    1. Park HS, Kim YJ, Yu MH, Choe WH, Jung SI, Jeon HJ. Three-Tesla magnetic resonance elastography for hepatic fibrosis: comparison with diffusion-weighted imaging and gadoxetic acid-enhanced magnetic resonance imaging. World J Gastroenterol. 2014;20:17558–17567. doi: 10.3748/wjg.v20.i46.17558.
    1. Ding Y, Rao SX, Meng T, Chen C, Li R, Zeng MS. Usefulness of T1 mapping on Gd-EOB-DTPA-enhanced MR imaging in assessment of non-alcoholic fatty liver disease. Eur Radiol. 2014;24:959–966. doi: 10.1007/s00330-014-3096-y.
    1. Lee NK, Kim S, Lee JW, et al. Biliary MR imaging with Gd-EOB-DTPA and its clinical applications. Radiographics. 2009;29:1707–1724. doi: 10.1148/rg.296095501.

Source: PubMed

3
Tilaa