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Online Appendices: GA-MRI for Secondary Liver Lesions

Online Supplemental Material

Manuscript: Comparative diagnostic accuracy of gadoxetic acid (Gd-EOB-DTPA) enhanced

MR imaging and contrast enhanced CT for the detection of liver metastases: A systematic

review and meta-analysis

Authors: Thomas D Vreugdenburg,1 PhD, Ning Ma,1 BHSc, BMaCompSc, Joanna K Duncan,1

PhD, Dagmara Riitano,1 BHSc (Hons), Alun L Cameron,1 PhD, Guy Maddern,1,2 MBBS, PhD

1Australian Safety and Efficacy Register of New Interventional Procedures – Surgical, Royal

Australasian College of Surgeons, Adelaide, South Australia, Australia

2Discipline of Surgery, University of Adelaide and The Queen Elizabeth Hospital, Adelaide,

South Australia, Australia

Corresponding author info:

Dr Thomas Vreugdenburg, ASERNIP-S

199 Ward Street, North Adelaide, SA 5006, Australia.

Email: [email protected]

Contents

Online Supplemental Material....................................................................1Appendix A – Search strategy..................................................................2Appendix B – QUADAS-II criteria............................................................4Appendix C – Quality appraisal of change in management studies........5Appendix D – Extracted diagnostic accuracy outcomes..........................6Appendix E – Excluded studies................................................................8Online Appendices Reference List.........................................................77

Vreugdenburg et al 2016 of 98

mailto:[email protected]


Appendix A – Search strategyTable 1 Search strategy

Search criteria Search terms

Population liver[MeSH Terms] OR liver OR liver neoplasms[MeSH] OR Carcinoma, hepatocellular[MeSH] OR “focal lesions”

Intervention Primovist OR Eovist OR Gd-EOB-DTPA OR “Gadolinium ethoxybenzyl dimeglumine” OR “Disodium gadoxetate” OR “Gadoxetic acid” OR “gadoxetic acid disodium” OR “gadoxetate disodium” OR “gadolinium ethoxybenzyl DTPA” OR gadolinium ethoxybenzyl DTPA [Supplementary Concept] OR

“Gadoxetic acid-enhanced MRI” OR “liver-specific agent” OR “contrast enhanced” OR “contrast-enhanced”

AND

MRI OR Magnetic Resonance Imag* OR Magnetic Resonance Imaging[MeSH Terms] OR DCE-MRI OR CE-MRI OR “magnetic resonance” OR “contrast-enhanced MRI” OR “contrast enhanced MRI”

Comparator(s) N/A

Outcomes N/A

Search limits Primovist was first referenced in the literature in 1991, therefore the search dates will be restricted to studies published since 1991.

Table 2 Bibliographic databases searched

Database with link to resource Period covered

Cochrane Library 1991 - 2015

PubMed 1991 - 2015

EMBASE 1991 - 2015

Current Contents Connect 1991 - 2015

TRIP database 1991 - 2015

The University of York Centre for Reviews and Dissemination 1991 - 2015

Table 3 Electronic internet databases searched

Database with link to resource Period covered

National Health Service (NHS) Evidence 1991 - 2015

National Guideline Clearinghouse 1991 - 2015

NZ Guideline Group 1991 - 2015

Guidelines International Network 1991 - 2015

BMJ best practice 1991 - 2015

Current Controlled Trials metaRegister 1991 - 2015

Australian New Zealand Clinical Trials Registry 1991 - 2015

ClinicalTrials.gov 1991 - 2015

MBS N/A

AIHW Hospital data 1991 - 2015


http://www.aihw.gov.au/hospitals-data/

http://www.mbsonline.gov.au/

http://clinicaltrials.gov/

http://www.anzctr.org.au/

http://controlled-trials.com/

http://bestpractice.bmj.com/best-practice/welcome.html

http://www.g-i-n.net/

http://www.health.govt.nz/about-ministry/ministry-health-websites/new-zealand-guidelines-group

http://www.guideline.gov/

http://www.evidence.nhs.uk/

http://www.crd.york.ac.uk/CRDWeb/

http://www.tripdatabase.com/

https://apps.webofknowledge.com/UA_GeneralSearch_input.do?product=UA&search_mode=GeneralSearch&SID=W1TXXe7UjHjiWPlyofY&preferencesSaved=

http://ovidsp.tx.ovid.com/sp-3.14.0b/ovidweb.cgi

http://www-ncbi-nlm-nih-gov.proxy.library.adelaide.edu.au/pubmed?holding=iauualib

http://www.cochranelibrary.com/


Royal Australasian College of Radiologists 1991 - 2015

American College of Radiology 1991 - 2015

Radiological Society of North America 1991 - 2015

Table 4 Health technology assessment Internet sites

Agency for Healthcare Research and Quality

Institute for Clinical and Economic Review (ICER)

The Canadian Agency for Drugs And Technologies in Health (CADTH)

NICE (NHS)


http://www.nice.org.uk/aboutnice/whatwedo/niceandthenhs/nice_and_the_nhs.jsp

http://www.cadth.ca/index.php/en/

http://www.icer-review.org/

http://www.ahrq.gov/index.html

http://www.rsna.org/

http://www.acr.org/

http://www.ranzcr.edu.au/


Appendix B – QUADAS-II criteria1. Was a consecutive or random sample of patients enrolled?

2. Was a case-control design avoided?

3. Did the study avoid inappropriate exclusions?

4. Is there concern that the included patients do not match the review question?

5. Were the index test results interpreted without knowledge of the results of the reference standard?

6. Were the index test results interpreted without knowledge of the results of a comparator test?

7. If a threshold was used, was it pre-specified?

8. Were the comparator test results interpreted without knowledge of the results of the reference standard?

9. Were the comparator test results interpreted without knowledge of the results of the index test?

10. If a threshold was used, was it pre-specified?

11. Is the reference standard likely to correctly classify the target condition?

12. Were the reference standard results interpreted without knowledge of the results of the index test?

13. Were the reference standard results interpreted without knowledge of the comparator test?

14. Was there an appropriate interval between index test(s) and reference standard? (<30 days)

15. Did all patients receive a reference standard?

16. Did patients receive the same reference standard?

17. Were all patients included in the analysis?



Appendix C – Quality appraisal of change in management studies

Table 3 Quality appraisal of direct evidence and change in management studies

Study (Author, Year) A.

Wer

e th

e el

igib

ility

crit

eria

sp

ecifi

ed?

B1. W

as ra

ndom

isat

ion

perfo

rmed

ad

equa

tely

?

B2. W

as tr

eatm

ent a

lloca

tion

conc

eale

d?

C. W

ere

the

grou

ps s

imila

r at

base

line?

D. W

ere

the

inde

x an

d co

ntro

l in

terv

entio

ns e

xplic

itly

desc

ribed

?

E. W

ere

co-in

terv

entio

ns a

void

ed o

r co

mpa

rabl

e?

F. W

as th

e pa

tient

blin

ded

to th

e in

terv

entio

n?

G. W

as th

e pr

ovid

er b

linde

d to

the

inte

rven

tion?

H. W

as th

e ou

tcom

e as

sess

or

blin

ded

to th

e in

terv

entio

n?

I. W

ere

the

outc

ome

mea

sure

s re

leva

nt?

J. W

ere

adve

rse

even

ts d

escr

ibed

?

K. W

as th

e wi

thdr

awal

/dro

pout

rate

de

scrib

ed a

nd a

ccep

tabl

e?

L1. W

as a

sho

rt-te

rm fo

llow-

up

mea

sure

men

t per

form

ed?

L2. W

as a

long

-term

follo

w-up

m

easu

rem

ent p

erfo

rmed

?

M. W

as th

e tim

ing

of th

e ou

tcom

e as

sess

men

t com

para

ble

in b

oth

grou

ps?

N. W

as th

e sa

mpl

e si

ze fo

r eac

h gr

oup

desc

ribed

?

O. D

id th

e an

alys

is in

clud

e an

in

tent

ion-

to-tr

eat a

naly

sis?

P. W

ere

poin

t est

imat

es a

nd

mea

sure

s of

var

iabi

lity

pres

ente

d fo

r th

e pr

imar

y ou

tcom

e m

easu

res?

Inte

rnal

val

idity

(sco

re fr

om 1

0)

Exte

rnal

val

idity

(sco

re fr

om 6

)

Cho et al. (2015) (1) NA NA NA NA X X NA 4 5

Kim et al. (2015) (2) NA NA NA NA X X NA 5 4

Patel et al. (2014) (3) NA NA NA NA X X X NA 4 4

Zech et al. (2014) (4) NA NA X X NA 6 5

NA = Not applicable or not possible because of the nature of the interventionInternal validity criteria: B, E, F, G, H, I, K, M, O; External validity criteria: A, C, D, J, L; Statistical criteria: N, PInternal validity: good ≥8, moderate 7-5, poor <5. External validity: good ≥ 5, moderate 3-4, poor<3



Appendix D – Extracted diagnostic accuracy outcomesTable 5 Per-lesion diagnostic accuracy of GA-MRI and CE-CT

Study (reference) Index Test Sensitivity (n) Specificity (n) PPV (n) NPV (n)

Chan et al. 2012 (5) GA-MRI 0.962 (51/53) N/A 0.910 (51/56) N/A

CE-CT 0.717 (38/53) N/A 0.880 (38/43) N/A

Kim et al. 2015 (2) GA-MRI* 0.952 (99/104) N/A 0.892 (99/111) N/A

CE-CT* 0.846 (88/104) N/A 0.727 (88/121) N/A

Kim et al. 2012 (6) GA-MRI* 0.973 (107/110) 0.980 (49/50) 0.991 (107/108) 0.942 (49/52)

CE-CT* 0.791 (87/110) 0.980 (49/50) 0.989 (87/88) 0.681 (49/72)

Lee et al. 2013 (10) GA-MRI* 0.869 (119/137) 0.802 (81/101) 0.856 (119/139) 0.818 (81/99)

CE-CT* 0.518 (119/137) 0.772 (78/101) 0.755 (71/94) 0.542 (78/144)

Motosugi et al. 2011 (9) GA-MRI† 0.935 (58/62) N/A 0.983 (58/59) N/A

CE-CT† 0.742 (46/62) N/A 0.979 (46/47) N/A

Muhi et al. 2011 (7) GA-MRI 0.949 (56/59) N/A 0.982 (56/57) N/A

CE-CT 0.634 (71/112) N/A 0.959 (71/74) N/A

Patel et al. 2014 (3) GA-MRI 1.000 (56/56) N/A 0.875 (56/64) N/A

CE-CT 0.804 (45/56) N/A 0.957 (45/47) N/A

Scharitzer et al. 2013 (8)

GA-MRI† 0.917 (88/96) N/A 0.898 (88/98) N/A

CE-CT† 0.833 (80/96) N/A 0.909 (80/88) N/A

Schulz et al. 2015 (11) GA-MRI 0.900 (126/140) 0.866 (175/202) 0.824 (126/153) 0.926 (175/189)

CE-CT 0.679 (95/140) 0.941 (190/202) 0.888 (95/107) 0.809 (190/235)CE-CT = contrast-enhanced computed tomography. GA-MRI = gadoxetate-enhanced magnetic resonance imaging. TP = true positive. FP = false positive. TN = true negative. FN = false negative. PPV = positive predictive value. NPV = negative predictive value. AUC = area under the curve. NR = not reported. N/A = not applicable.* results averaged across two readers† results averaged across three readers

Table 6 Per-lesion diagnostic accuracy of GA-MRI and CE-CT for lesions smaller than 10mm


Kim et al. 2015 (2) GA-MRI* 0.857 (24/28) N/A 0.727 (24/33) N/A

CE-CT* 0.500 (14/28) N/A 0.326 (14/43) N/A

Lee et al. 2013 (10) GA-MRI* 0.810 (64/79) 0.773 (58/75) 0.790 (64/81) 0.795 (58/73)

CE-CT* 0.266 (21/79) 0.827 (62/75) 0.618 (21/34) 0.517 (62/120)

Motosugi et al. 2011 (9) GA-MRI† 0.905 (38/42) N/A 0.974 (38/39) N/A

CE-CT† 0.619 (26/42) N/A 0.963 (26/27) N/A

Muhi et al. 2011 (7) GA-MRI 0.923 (24/26) N/A 1.000 (24/24) N/A

CE-CT 0.260 (13/50) N/A 0.929 (13/14) N/A

Scharitzer et al. 2013 (8) GA-MRI† 0.806 (25/31) N/A N/A N/A

CE-CT† 0.645 (20/31) N/A N/A N/A


CE-CT 0.163 (7/43) 0.961 (147/153) 0.538 (7/13) 0.803 (147/183)CE-CT = contrast-enhanced computed tomography. GA-MRI = gadoxetate-enhanced magnetic resonance imaging. TP = true positive. FP = false positive. TN = true negative. FN = false negative. PPV = positive predictive value. NPV = negative predictive value. AUC = area under the curve. NR = not reported. N/A = not applicable.* results are averaged across two readers



† results are averaged across three readers

Table 7 Per-patient diagnostic accuracy of GA-MRI and CE-CT


Kim et al. 2012 (6) GA-MRI* 0.939 (46/49) 1.000 (18/18) 1.000 (46/46) 0.857 (18/21)

CE-CT* 0.653 (32/49) 1.000 (18/18) 1.000 (32/32) 0.514 (18/35)

Lee et al. 2013 (10) GA-MRI* 0.941 (48/51) 0.823 (51/62) 0.814 (48/59) 0.994 (51/54)

CE-CT* 0.784 (40/51) 0.726 (45/62) 0.702 (40/57) 0.804 (45/56)

Motosugi et al. 2011 (9)

GA-MRI† 0.800 (12/15) 0.974 (38/39) 0.923 (12/13) 0.927 (38/41)

CE-CT† 0.600 (9/15) 0.974 (38/39) 0.900 (9/10) 0.864 (38/44)


CE-CT 0.929 (39/42) 0.500 (2/4) 0.951 (39/41) 0.400 (2/5)CE-CT = contrast-enhanced computed tomography. GA-MRI = gadoxetate-enhanced magnetic resonance imaging. TP = true positive. FP = false positive. TN = true negative. FN = false negative. PPV = positive predictive value. NPV = negative predictive value. AUC = area under the curve. NR = not reported. N/A = not applicable.* results are averaged across two readers† results are averaged across three readers



Appendix E – Excluded studies

Inappropriate population1. Adam, G, Neuerburg, J, Spuntrup, E, Muhler, A, Scherer, K &

Gunther, RW 1994, 'Dynamic contrast-enhanced mr imaging of the upper abdomen: Enhancement properties of gadobutrol, gadolinium-dtpa-polylysine, and gadolinium-dtpa-cascade-polymer', Magn Reson Med, vol.32(5), pp. 622-8.

2. Akai, H, Kiryu, S, Matsuda, I, Satou, J, Takao, H, Tajima, T, Watanabe, Y, Imamura, H, Kokudo, N, Akahane, M & Ohtomo, K 2011, 'Detection of hepatocellular carcinoma by gd-eob-dtpa-enhanced liver mri: Comparison with triple phase 64 detector row helical ct', Eur J Radiol, vol.80(2), pp. 310-5.

3. Alaboudy, A, Inoue, T, Hatanaka, K, Chung, H, Hyodo, T, Kumano, S, Murakami, T, Moustafa, EF & Kudo, M 2011, 'Usefulness of combination of imaging modalities in the diagnosis of hepatocellular carcinoma using sonazoid(r)-enhanced ultrasound, gadolinium diethylene-triamine-pentaacetic acid-enhanced magnetic resonance imaging, and contrast-enhanced computed tomography', Oncology, vol.81 Suppl 1pp. 66-72.

4. Alegre Castellanos, A, Molina Granados, JF, Escribano Fernandez, J, Gallardo Munoz, I & Trivino Tarradas Fde, A 2012, 'Early phase detection of bile leak after hepatobiliary surgery: Value of gd-eob-dtpa-enhanced mr cholangiography', Abdom Imaging, vol.37(5), pp. 795-802.

5. Baek, CK, Choi, JY, Kim, KA, Park, MS, Lim, JS, Chung, YE, Kim, MJ & Kim, KW 2012, 'Hepatocellular carcinoma in patients with chronic liver disease: A comparison of gadoxetic acid-enhanced mri and multiphasic MD-CT', Clin Radiol, vol.67(2), pp. 148-56.

6. Balci, NC, Inan, N, Anik, Y, Erturk, MS, Ural, D & Demirci, A 2006, 'Low-dose gadobenate dimeglumine versus standard-dose gadopentate dimeglumine for delayed contrast-enhanced cardiac magnetic resonance imaging', Academic Radiology, vol.13(7), pp. 833-39.

7. Bluemke, DA, Sahani, D, Amendola, M, Balzer, T, Breuer, J, Brown, JJ, Casalino, DD, Davis, PL, Francis, IR, Krinsky, G, Lee, FT, Lu, D, Paulson, EK, Schwartz, LH & Siegelman, ES 2005, 'Efficacy and safety of mr imaging with liver-specific contrast agent: Us multicenter phase iii study', Radiology, vol.237(1), pp. 89-98.

8. Bohte, AE, van Werven, JR, Bipat, S & Stoker, J 2011, '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, vol.21(1), pp. 87-97.

9. Bottcher, J, Hansch, A, Pfeil, A, Schmidt, P, Malich, A, Schneeweiss, A, Maurer, MH, Streitparth, F, Teichgraber, UK & Renze, DM



2013, 'Detection and classification of different liver lesions: Comparison of gd-eob-dtpa-enhanced mri versus multiphasic spiral ct in a clinical single centre investigation', Eur J Radiol, vol.82(11), pp. 1860-69.

10. Bremer, C, Spiegel, HU, Allkemper, T, Reimer, P, Rummeny, EJ & Peters, PE 1995, 'Contrast-enhanced magnetic resonance imaging with intracellular contrast agents-a new way of monitoring hepatic reperfusion injury?', Transplant Proc, vol.27(5), pp. 2849-51.

11. Castellanos, AA, Granados, JFM, Fernandez, JE, Munoz, IG & De Asis Trivino Tarradas, F 2012, 'Early phase detection of bile leak after hepatobiliary surgery: Value of gd-eob-dtpaenhanced mr cholangiography', Abdominal Imaging, vol.37(5), pp. 795-802.

12. Cha, DI, Lee, MW, Kim, YK, Kim, SH, Park, HJ, Rhim, H & Lim, HK 2014, 'Assessing patients with hepatocellular carcinoma meeting the milan criteria: Is liver 3 tesla mr with gadoxetic acid necessary in addition to liver ct?', J Magn Reson Imaging, vol.39(4), pp. 842-52.

13. Chen, L, Zhang, L, Liang, M, Bao, J, Zhang, J, Xia, Y, Huang, X & Wang, J 2014, 'Magnetic resonance imaging with gadoxetic acid disodium for the detection of hepatocellular carcinoma: A meta-analysis of 18 studies', Acad Radiol, vol.21(12), pp. 1603-13.

14. Choi, SH, Byun, JH, Kwon, HJ, Ha, HI, Lee, SJ, Kim, SY, Won, HJ & Kim, PN 2015, 'The usefulness of gadoxetic acid-enhanced dynamic magnetic resonance imaging in hepatocellular carcinoma: Toward improved staging', Ann Surg Oncol, vol.22(3), pp. 819-25.

15. Di Martino, M, Marin, D, Guerrisi, A, Baski, M, Galati, F, Rossi, M, Brozzetti, S, Masciangelo, R, Passariello, R & Catalano, C 2010, 'Intraindividual comparison of gadoxetate disodium - enhanced mr imaging and 64-section multidetector ct in the detection of hepatocellular carcinoma in patients with cirrhosis', Radiology, vol.256(3), pp. 806-16.

16. Eadie, LH, Taylor, P & Gibson, AP 2012, 'A systematic review of computer-assisted diagnosis in diagnostic cancer imaging', Eur J Radiol, vol.81(1), pp. e70-e76.

17. Filippone, A, Cianci, R, Iezzi, R, Legnini, M & Storto, ML 2009, 'Effect of clinical history in focal liver lesion detection and classification on 4-detector row computed tomography and gadoxetic acid enhanced mr imaging in oncologic patients', J Comput Assist Tomogr, vol.33(6), pp. 851-7.

18. Fujimoto, K, Kuroda, JI, Makino, K, Hasegawa, Y & Kuratsu, JI 2013, 'Skull metastasis from intrahepatic cholangiocarcinoma: Report of 3 cases and review of the literature', Neurologia Medico-Chirurgica, vol.53(10), pp. 717-21.



19. Halavaara, J, Breuer, J, Ayuso, C, Balzer, T, Bellin, MF, Blomqvist, L, Carter, R, Grazioli, L, Hammerstingl, R, Huppertz, A, Jung, G, Krause, D, Laghi, A, Leen, E, Lupatelli, L, Marsili, L, Martin, J, Pretorius, ES, Reinhold, C, Stiskal, M & Stolpen, AH 2006, 'Liver tumor characterization: Comparison between liver-specific gadoxetic acid disodium-enhanced mri and biphasic ct-a multicenter trial', J Comput Assist Tomogr, vol.30(3), pp. 345-54.

20. Hammerstingl, R, Huppertz, A, Breuer, J, Balzer, T, Blakeborough, A, Carter, R, Fuste, LC, Heinz-Peer, G, Judmaier, W, Laniado, M, Manfredi, RM, Mathieu, DG, Muller, D, Mortele, K, Reimer, P, Reiser, MF, Robinson, PJ, Shamsi, K, Strotzer, M, Taupitz, M, Tombach, B, Valeri, G, van Beers, BE & Vogl, TJ 2008, 'Diagnostic efficacy of gadoxetic acid (primovist®)-enhanced mri and spiral ct for a therapeutic strategy: Comparison with intraoperative and histopathologic findings in focal liver lesions', Eur Radiol, vol.18(3), pp. 457-67.

21. Haradome, H, Grazioli, L, Tinti, R, Morone, M, Motosugi, U, Sano, K, Ichikawa, T, Kwee, TC & Colagrande, S 2011, 'Additional value of gadoxetic acid-dtpa-enhanced hepatobiliary phase mr imaging in the diagnosis of early-stage hepatocellular carcinoma: Comparison with dynamic triple-phase multidetector ct imaging', J Magn Reson Imaging, vol.34(1), pp. 69-78.

22. Hirakawa M, YK, Irie H, Tajima T, Nishie A, Asayama Y, Ishigami K, Kakihara D, Taketomi A, Aishima S, Honda H. 2011, 'Performance of radiological methods in diagnosing hepatocellular carcinoma preoperatively in a recipient of living related liver transplantation: Comparison with step section histopathology.', Jpn J Radiol, vol.29(2), pp. 129-37.

23. Hwang, J, Kim, SH, Kim, YS, Lee, MW, Woo, JY, Lee, WJ & Lim, HK 2010, 'Gadoxetic acid-enhanced mri versus multiphase multidetector row computed tomography for evaluating the viable tumor of hepatocellular carcinomas treated with image-guided tumor therapy', J Magn Reson Imaging, vol.32(3), pp. 629-38.

24. Hwang, J, Kim, SH, Lee, MW & Lee, JY 2012, 'Small (</= 2 cm) hepatocellular carcinoma in patients with chronic liver disease: Comparison of gadoxetic acid-enhanced 3.0 t mri and multiphasic 64-multirow detector ct', Br J Radiol, vol.85(1015), pp. e314-22.

25. Ichikawa, T, Saito, K, Yoshioka, N, Tanimoto, A, Gokan, T, Takehara, Y, Kamura, T, Gabata, T, Murakami, T, Ito, K, Hirohashi, S, Nishie, A, Saito, Y, Onaya, H, Kuwatsuru, R, Morimoto, A, Ueda, K, Kurauchi, M & Breuer, J 2010, 'Detection and characterization of focal liver lesions a japanese phase iii, multicenter comparison between gadoxetic acid disodium-enhanced magnetic resonance imaging and contrast-enhanced computed tomography predominantly in patients with hepatocellular carcinoma and chronic liver disease', Invest Radiol, vol.45(3), pp. 133-41.



26. Junqiang, L, Yinzhong, W, Li, Z, Shunlin, G, Xiaohui, W, Yanan, Z & Kehu, Y 2014, 'Gadoxetic acid disodium (gd-eobdtpa)-enhanced magnetic resonance imaging for the detection of hepatocellular carcinoma: A meta analysis', J Magn Reson Imaging, vol.39(5), pp. 1079-87.

27. Kakihara, D, Nishie, A, Harada, N, Shirabe, K, Tajima, T, Asayama, Y, Ishigami, K, Nakayama, T, Takayama, Y, Okamoto, D, Fujita, N, Kishimoto, J & Honda, H 2013, 'Performance of gadoxetic acid-enhanced mri for detecting hepatocellular carcinoma in recipients of living-related-liver-transplantation: Comparison with dynamic multidetector row computed tomography and angiography-assisted computed tomography', J Magn Reson Imaging, vol.40(5), pp. 1112-20.

28. Kawada, N, Ohkawa, K, Tanaka, S, Matsunaga, T, Uehara, H, Ioka, T, Takano, Y, Takakura, R, Imanaka, K, Tamai, C, Kawaguchi, T, Tomita, Y, Nakanishi, K & Katayama, K 2010, 'Improved diagnosis of well-differentiated hepatocellular carcinoma with gadolinium ethoxybenzyl diethylene triamine pentaacetic acid-enhanced magnetic resonance imaging and sonazoid contrast-enhanced ultrasonography', Hepatol Res, vol.40(9), pp. 930-6.

29. Kidney, DD, Dietrich, RB, Goyal, AK, Yan, K & Bradley, WG 1998, 'Mri of extracranial masses in children: The usefulness of gadolinium-chelate enhancement', Pediatric Radiology, vol.28(5), pp. 322-28.

30. Kim, SH, Kim, SH, Lee, J, Kim, MJ, Jeon, YH, Park, Y, Choi, D, Lee, WJ & Lim, HK 2009b, 'Gadoxetic acid-enhanced mri versus triple-phase MD-CT for the preoperative detection of hepatocellular carcinoma', Am J Roentgenol, vol.192(6), pp. 1675-81.

31. Kim, YK, Kim, CS, Han, YM, Kwak, HS, Jin, GY, Hwang, SB, Chung, GH, Lee, SY & Yu, HC 2009a, 'Detection of hepatocellular carcinoma: Gadoxetic acid-enhanced 3-dimensional magnetic resonance imaging versus multi-detector row computed tomography', J Comput Assist Tomogr, vol.33(6), pp. 844-50.

32. Kim, H-D, Lim, Y-S, Han, S, An, J, Kim, G, Kim, SY, Lee, SJ, Won, HJ & Byun, JH 2015, 'Evaluation of early-stage hepatocellular carcinoma by magnetic resonance imaging with gadoxetic acid detects additional lesions and increases overall survival', Gastroenterology, vol.pp.

33. Lee, KY, Masi, JN, Sell, CA, Schier, R, Link, TM, Steinbach, LS, Safran, M, Ma, B & Majumdar, S 2005, 'Computer-aided quantification of focal cartilage lesions using mri: Accuracy and initial arthroscopic comparison', Osteoarthritis and Cartilage, vol.13(8), pp. 728-37.

34. Lee, CH, Kim, KA, Lee, J, Park, YS, Choi, JW & Park, CM 2012, 'Using low tube voltage (80 kvp) quadruple phase liver ct for the detection of hepatocellular carcinoma: Two-year experience and



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2. Queiroz, MR, Francisco Neto, MJ, Garcia, RG, Rahal Junior, A, Salvalaggio, P & Funari, MB 2013, 'High correlation between microbubble contrast-enhanced ultrasound, magnetic resonance and histopathology in the evaluation of hepatocellular carcinoma', Einstein (Sao Paulo), vol.11(4), pp. 500-6.

No full-text available1. Hayes 2010, Eovist (bayer schering pharma ag) contrast agent for

magnetic resonance imaging of the liver, viewed <http://www.crd.york.ac.uk/CRDWeb/ShowRecord.asp?AccessionNumber=32010000940>.

2. Hayes 2013, Magnetic resonance elastography for detecting and staging liver fibrosis, viewed <http://www.crd.york.ac.uk/crdweb/ShowRecord.asp?ID=32013000300>.

Duplicate data reported in other publications 1. Jung, G, Breuer, J, Poll, LW, Koch, JA, Balzer, T, Chang, S & Modder,

U 2006, 'Imaging characteristics of hepatocellular carcinoma using the hepatobiliary contrast agent gd-eob-dtpa', Acta Radiol, vol.47(1), pp. 15-23.



Online Appendices Reference List1. Cho JY, Lee YJ, Han HS, Yoon YS, Kim J, Choi Y, et al. Role of

gadoxetic acid-enhanced magnetic resonance imaging in the preoperative evaluation of small hepatic lesions in patients with colorectal cancer. World J Surg 2015; 39: 1-6.

2. Kim HJ, Lee SS, Byun JH, Kim JC, Yu CS, Park SH, et al. Incremental Value of Liver MR Imaging in Patients with Potentially Curable Colorectal Hepatic Metastasis Detected at CT: A Prospective Comparison of Diffusion-weighted Imaging, Gadoxetic Acid-enhanced MR Imaging, and a Combination of Both MR Techniques. Radiol 2015; 274: 712-22.

3. Patel S, Cheek S, Osman H, Jeyarajah D. MRI with gadoxetate disodium for colorectal liver metastasis: Is it the new "imaging modality of choice"? J Gastrointest Surg 2014; 18: 2130-5.

4. Zech CJ, Korpraphong P, Huppertz A, Denecke T, Kim MJ, Tanomkiat W, et al. Randomized multicentre trial of gadoxetic acid-enhanced MRI versus conventional MRI or CT in the staging of colorectal cancer liver metastases. Br J Surg 2014; 101: 613-21.

5. Chan VO, Das JP, Gerstenmaier JF, Geoghegan J, Gibney RG, Collins CD, et al. Diagnostic performance of MDCT, PET/CT and gadoxetic acid (Primovist(R))-enhanced MRI in patients with colorectal liver metastases being considered for hepatic resection: initial experience in a single centre. Ir J Med Sci 2012; 181: 499-509.

6. Kim YK, Park G, Kim CS, Yu HC, Han YM. Diagnostic efficacy of gadoxetic acid-enhanced MRI for the detection and characterisation of liver metastases: comparison with multidetector-row CT. Br J Radiol 2012; 85: 539-47.

7. Muhi A, Ichikawa T, Motosugi U, Sou H, Nakajima H, Sano K, et al. Diagnosis of colorectal hepatic metastases: comparison of contrast-enhanced CT, contrast-enhanced US, superparamagnetic iron oxide-enhanced MRI, and gadoxetic acid-enhanced MRI. J Magn Reson Imaging 2011; 34: 326-35.

8. Scharitzer M, Ba-Ssalamah A, Ringl H, Kolblinger C, Grunberger T, Weber M, et al. Preoperative evaluation of colorectal liver metastases: comparison between gadoxetic acid-enhanced 3.0-T MRI and contrast-enhanced MDCT with histopathological correlation. Eur Radiol 2013; 23: 2187-96.

9. Motosugi U, Tomoaki Ichikawa M, PhD, Hiroyuki Morisaka M, Hironobu Sou M, Ali Muhi M, PhD, Kazufumi Kimura M, et al. Detection of pancreatic carcinoma and liver metastases with gadoxetic acid-enhanced MR imaging: Comparison with contrast-enhanced multi-detector row CT. Radiol 2011; 260: 446-53.

10. Lee KH, Lee JM, Park JH, Kim JH, Park HS, Yu MH, et al. MR imaging in patients with suspected liver metastases: value of liver-specific contrast agent gadoxetic acid. Korean J Radiol 2013; 14: 894-904.



11. Schulz A, Viktil E, Godt JC, Johansen CK, Dormagen JB, Holtedahl JE, et al. Diagnostic performance of CT, MRI and PET/CT in patients with suspected colorectal liver metastases: the superiority of MRI. Acta Radiol 2015.


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