Superparamagnetic iron oxide-enhanced magnetic resonance imaging for focal hepatic lesions: Systematic review and meta-analysis

Table 1 Characteristics of 15 studies included in the meta-analysis

Ref.	Year	Country	Subject					MRI				Result
			Patients (n)	Age (yr)	Lesions (n)	Lesion type	Size (cm)	Type	Sequence	Contrast agent	Dose	Iso-/hypo	Hyper-
Harisinghani et al[12]	1997	United States	35	46	15	Hemangioma	NC	1.5T	T2WI	Code-7227	1.1 mg Fe/kg	13	2
					17	Metastases	NC					0	17
					6	HCC	NC					2	4
Imai et al[19]	2000	Japan	27	62	6	DN	1.6	1.5T	T2*WI	Ferumoxide	10 μmol/kg	6	0
					13	WD-HCC	1.6					11	2
					10	MD-HCC	1.6					0	10
					8	PD-HCC	1.6					0	8
Lim et al[15]	2001	South Korea	68	51	10	WD-HCC	2.1	1.5T	T2*WI	Ferumoxide	15 μmol/kg	6	4
					69	MDPD-HCC	5.3					0	69
					19	DN	0.8					19	0
Zheng et al[11]	2002	China	43	51	22	HCC	< 3	1.5T	T2WI	Feridex	0.05 mL/kg	0	22
					7	Other malignancy	< 3					0	7
					4	Cirrhotic nodules	< 3					4	0
					5	Hemangioma						0	5
					5	FNH						0	5
					4	Others						0	4
Zhang et al[20]	2003	China	30	50	30	HCCs	NC	0.5T	T2WI	Feridex	0.56 mL/kg	0	30
					6	Regenerative nodules						6	0
Suzuki et al[21]	2004	Japan	45	66	41	HCCs	2.26	1.5T	T2*WI	Ferumoxide	0.05 mL/kg	7	34
					11	Benign						10	1
Kato et al[22]	2004	Japan	43	66	17	WD-HCC	3.00	1.5T	T2*WI	Ferumoxide	10 mmol/kg	4	13
					28	MD-HCC	3.00					1	27
					6	PD-HCC	3.20					0	6
Inoue et al[24]	2005	Japan	49	67	20	WD-HCC	2.70	1.5T	T2*WI	Ferumoxide	0.016 mL/kg	4	16
					20	MDPD-HCC						0	20
					9	DNs						8	1
Kobayashi et al[9]	2007	Japan	10	45	6	DNs	NC	1.5T	T2WI	Ferucarbotran	NC	6	0
					4	HCC						0	4
Park et al[18]	2009	South Korea	114	55	37	WD-HCC	2.38	3.0T	T2*WI	Ferucarbotran	8 mmol/kg	20	17
					156	MDPD-HCC	4.10					6	149
					23	DNs	1.28					22	1
Macarini et al[7]	2009	Italy	22	53	14	HCC	1.70	1.5T	T2*WI	Ferumoxide	NC	0	14
					3	WD-HCC
					11	MDPD-HCC
					4	DN with HCC	2.10					0	4
					39	DNs	0.80					39	0
					2	Cystadenoma	1.20					2	0
Yoon et al[16]	2009	South Korea	28	51	33	DNs	1.31	3.0T	T2*WI	Ferucarbotran	1.4 mL, ≥ 60 kg	25	8
					32	WD-HCC	1.79				0.9 mL, < 60 kg	13	19
Yoo et al[8]	2009	South Korea	108	56	124	HCCs	3.00	3.0T	T2*WI	Ferucarbotran	1.4 mL, ≥ 60 kg	16	108
					28	DNs					0.9 mL, < 60 kg	25	3
Okada et al[23]	2010	Japan	36	69	22	WD-HCC	1.40	1.5T	T2*WI	Ferucarbotran	0.45 mg Fe/kg	15	7
					15	MDPD-HCC	2.40					0	15
					4	DNs	1.60					4	0
Chou et al[25]	2011	Taiwan	12	56	11	HCC	2.30	1.5T	T2*WI	Ferucarbotran	1.4 mL, > 50 kg	3	8
					6	Benign	1.60					6	0

DN: Nodular dysplasia; FNH: Focal nodular hyperplasia; HCC: Hepatocellular carcinoma; hyper: Hyperintensity; iso-/hypo: Isointensity/hypointensity; MD: Moderately-differentiated, NC: Not clear; PD: Poorly-differentiated; WD: Well-differentiated; MRI: Magnetic resonance imaging.

Table 2 Quality assessment of diagnostic accuracy studies scores¹ for each included study

Ref.	QUADAS items
	1	2	3	4	5	6	7	8	9	10	11	12	13
Zheng et al[11]	0	1	0	0.5	0	0	1	0	0.5	0.5	0.5	1	1
Imai et al[19]	1	1	1	0.5	1	1	1	0	1	0.5	0.5	1	1
Lim et al[15]	1	1	1	0.5	1	1	1	1	0.5	1	0.5	1	1
Zhang et al[20]	1	1	1	0.5	1	1	1	0	0.5	1	0.5	1	1
Inoue et al[24]	1	1	1	0.5	1	1	1	1	0.5	1	0.5	1	1
Park et al[18]	1	1	1	0.5	1	1	1	1	0	0.5	0.5	1	1
Macarini et al[7]	1	1	1	1	1	1	1	0	1	0.5	0.5	1	1
Yoon et al[16]	1	1	1	0.5	1	1	1	1	1	1	0.5	1	1
Harisinghani et al[12]	1	1	1	0.5	0	1	1	1	1	0.5	0.5	1	1
Yoo et al[8]	1	1	1	0.5	1	1	1	1	0	0.5	0.5	1	1
Suzuki et al[21]	1	1	1	0.5	1	1	1	0	0.5	0.5	0.5	1	1
Kobayashi et al[9]	1	1	1	0.5	1	1	1	0	1	0.5	0.5	1	1
Kato et al[22]	1	1	1	1	1	1	1	1	1	0	0.5	1	1
Okada et al[23]	1	1	1	0.5	1	1	1	0.5	0.5	1	1	1	1
Chou et al[25]	1	1	1	1	1	1	1	0	0.5	0.5	0.5	1	1

¹1 = yes; 0 = no; 0.5 = unclear. Quality assessment of diagnostic accuracy studies (QUADAS) items: (1) Was the spectrum of a patient representative of the patients who will receive the test in practice? (2) Were the selection criteria clearly described? (3) Is the reference standard likely to correctly classify the target condition? (4) Is the time period between the index test and reference standard short enough to ensure that the target condition did not change between the two tests? (5) Did the whole sample or a random selection of the sample receive verification using a reference standard of diagnosis? (6) Did patients receive the same reference standard regardless of the index test result? (7) Was the execution of the index test described in sufficient detail to permit replication of the test? (8) Was the execution of the reference standard test described in sufficient detail to permit its replication? (9) Were the index test results interpreted without knowledge of the results of the reference standard? (10) Were the reference standard results interpreted without knowledge of the results of the index test? (11) Were the same clinical data available when the test results were interpreted as would be available when the test is used in clinical practice? (12) Were uninterpretable or intermediate test results reported? (13) Were withdrawals from the study explained?

Table 3 Assessment of the threshold effect in all accuracy studies

Weighted regression (inverse variance)
Variable	Coefficient	SE	t	P value
a	3.643	0.548	6.652	0.0000
b(1)	-0.239	0.314	0.760	0.4617

τ² = 2.3703 (convergence is achieved after five iterations); Restricted Maximum Likelihood estimation (REML). n = 14; Filter OFF; Add 0.5 to all cells of the studies with zero. Spearman correlation coefficient: -0.266, P = 0.358; Logit (true positive rate) vs Logit (false positive rate); Moses’ model (D = a + bS).