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Double-Contrast MRI for Accurate Staging of Hepatocellular Carcinoma in Patients with Cirrhosis

Robert F. Hanna1, Norbert Kased1, Sharon W. Kwan1, Anthony C. Gamst1, Agnes C. Santosa1, Tarek Hassanein2 and Claude B. Sirlin1

1 Department of Radiology, Division of Body Imaging, University of California, San Diego, 200 W Arbor Dr., San Diego, CA 92103-8756.
2 Department of Internal Medicine, University of California, San Diego, San Diego, CA.


Figure 1
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Fig. 1 —Flow diagram depicts manner in which patients were selected. Top three boxes describe procedures completed for clinical care. Bottom five boxes describe procedures completed for research study. Inclusion criteria were double-contrast MRI performed, cirrhosis histologically confirmed, and liver explant examined after double-contrast MRI examination. Exclusion criteria were ablative therapy before study MRI and liver explant performed more than 12 months after MRI in patients in whom explant had positive results for hepatocellular carcinoma (HCC). For patients in whom explant had negative results for HCC, MRI-explant interval greater than 12 months was acceptable, and such patients were not excluded.

 

Figure 2
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Fig. 2 —Graph depicts degree of understaging and overstaging by each radiologist for all 48 patients with cirrhosis. MRI staging accuracy is determined by subtracting pathologic tumor stage from MRI tumor stage for each radiologist. Negative values indicate understaging with MRI; positive values indicate overstaging. For example, -2 represents understaging by two stages; 0, correct staging. *For both radiologist 1 and radiologist 2, one patient had disease understaged by four stages owing to undetected vascular invasion.

 

Figure 3
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Fig. 3A —Receiver operating characteristic curves. Plots depict curves for each radiologist on per-patient (A) and per-lesion (B) basis. Per-patient and per-lesion areas under curve are shown in Table 4.

 

Figure 4
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Fig. 3B —Receiver operating characteristic curves. Plots depict curves for each radiologist on per-patient (A) and per-lesion (B) basis. Per-patient and per-lesion areas under curve are shown in Table 4.

 

Figure 5
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Fig. 4A —51-year-old man with hypervascular hepatocellular carcinoma (HCC) in pathologic stage T2. Two nodules measuring 23 (black arrows) and 24 (white arrows) mm are present in segments V and III of liver. Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) MR images before gadolinium administration (A) and during hepatic arterial (B), portal venous (C), and equilibrium (D) phases after gadolinium administration show both nodules are enhanced in arterial phase (B) and wash out to become hypointense relative to surrounding liver in equilibrium phase (D). Degree of arterial phase enhancement is greater for segment III than segment V nodule.

 

Figure 6
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Fig. 4B —51-year-old man with hypervascular hepatocellular carcinoma (HCC) in pathologic stage T2. Two nodules measuring 23 (black arrows) and 24 (white arrows) mm are present in segments V and III of liver. Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) MR images before gadolinium administration (A) and during hepatic arterial (B), portal venous (C), and equilibrium (D) phases after gadolinium administration show both nodules are enhanced in arterial phase (B) and wash out to become hypointense relative to surrounding liver in equilibrium phase (D). Degree of arterial phase enhancement is greater for segment III than segment V nodule.

 

Figure 7
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Fig. 4C —51-year-old man with hypervascular hepatocellular carcinoma (HCC) in pathologic stage T2. Two nodules measuring 23 (black arrows) and 24 (white arrows) mm are present in segments V and III of liver. Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) MR images before gadolinium administration (A) and during hepatic arterial (B), portal venous (C), and equilibrium (D) phases after gadolinium administration show both nodules are enhanced in arterial phase (B) and wash out to become hypointense relative to surrounding liver in equilibrium phase (D). Degree of arterial phase enhancement is greater for segment III than segment V nodule.

 

Figure 8
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Fig. 4D —51-year-old man with hypervascular hepatocellular carcinoma (HCC) in pathologic stage T2. Two nodules measuring 23 (black arrows) and 24 (white arrows) mm are present in segments V and III of liver. Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) MR images before gadolinium administration (A) and during hepatic arterial (B), portal venous (C), and equilibrium (D) phases after gadolinium administration show both nodules are enhanced in arterial phase (B) and wash out to become hypointense relative to surrounding liver in equilibrium phase (D). Degree of arterial phase enhancement is greater for segment III than segment V nodule.

 

Figure 9
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Fig. 4E —51-year-old man with hypervascular hepatocellular carcinoma (HCC) in pathologic stage T2. Two nodules measuring 23 (black arrows) and 24 (white arrows) mm are present in segments V and III of liver. Superparamagnetic iron oxide-enhanced 2D SPGR images obtained before administration of gadolinium with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image with TE of 90 milliseconds (H) show both lesions have high signal intensity suggestive of phagocyte depletion. Each radiologist correctly diagnosed both HCC nodules and staged HCC burden.

 

Figure 10
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Fig. 4F —51-year-old man with hypervascular hepatocellular carcinoma (HCC) in pathologic stage T2. Two nodules measuring 23 (black arrows) and 24 (white arrows) mm are present in segments V and III of liver. Superparamagnetic iron oxide-enhanced 2D SPGR images obtained before administration of gadolinium with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image with TE of 90 milliseconds (H) show both lesions have high signal intensity suggestive of phagocyte depletion. Each radiologist correctly diagnosed both HCC nodules and staged HCC burden.

 

Figure 11
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Fig. 4G —51-year-old man with hypervascular hepatocellular carcinoma (HCC) in pathologic stage T2. Two nodules measuring 23 (black arrows) and 24 (white arrows) mm are present in segments V and III of liver. Superparamagnetic iron oxide-enhanced 2D SPGR images obtained before administration of gadolinium with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image with TE of 90 milliseconds (H) show both lesions have high signal intensity suggestive of phagocyte depletion. Each radiologist correctly diagnosed both HCC nodules and staged HCC burden.

 

Figure 12
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Fig. 4H —51-year-old man with hypervascular hepatocellular carcinoma (HCC) in pathologic stage T2. Two nodules measuring 23 (black arrows) and 24 (white arrows) mm are present in segments V and III of liver. Superparamagnetic iron oxide-enhanced 2D SPGR images obtained before administration of gadolinium with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image with TE of 90 milliseconds (H) show both lesions have high signal intensity suggestive of phagocyte depletion. Each radiologist correctly diagnosed both HCC nodules and staged HCC burden.

 

Figure 13
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Fig. 5A —53-year-old woman with pathologic tumor stage T2 hypovascular hepatocellular carcinoma (one 23-mm nodule in segment II). Both radiologists detected lesion and correctly assigned MRI tumor stage of T2. Asterisk indicates ascites. Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) MR image before gadolinium administration shows high signal intensity facilitating recognition of nodule (arrow).

 

Figure 14
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Fig. 5B —53-year-old woman with pathologic tumor stage T2 hypovascular hepatocellular carcinoma (one 23-mm nodule in segment II). Both radiologists detected lesion and correctly assigned MRI tumor stage of T2. Asterisk indicates ascites. Dynamic 3D T1-weighted transverse fat-saturated SPGR MR images in hepatic arterial (B), portal venous (C), and equilibrium (D) phases after gadolinium administration show poor visibility of hepatocellular carcinoma nodule (arrows). Minimal enhancement of nodule is evident in B.

 

Figure 15
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Fig. 5C —53-year-old woman with pathologic tumor stage T2 hypovascular hepatocellular carcinoma (one 23-mm nodule in segment II). Both radiologists detected lesion and correctly assigned MRI tumor stage of T2. Asterisk indicates ascites. Dynamic 3D T1-weighted transverse fat-saturated SPGR MR images in hepatic arterial (B), portal venous (C), and equilibrium (D) phases after gadolinium administration show poor visibility of hepatocellular carcinoma nodule (arrows). Minimal enhancement of nodule is evident in B.

 

Figure 16
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Fig. 5D —53-year-old woman with pathologic tumor stage T2 hypovascular hepatocellular carcinoma (one 23-mm nodule in segment II). Both radiologists detected lesion and correctly assigned MRI tumor stage of T2. Asterisk indicates ascites. Dynamic 3D T1-weighted transverse fat-saturated SPGR MR images in hepatic arterial (B), portal venous (C), and equilibrium (D) phases after gadolinium administration show poor visibility of hepatocellular carcinoma nodule (arrows). Minimal enhancement of nodule is evident in B.

 

Figure 17
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Fig. 5E —53-year-old woman with pathologic tumor stage T2 hypovascular hepatocellular carcinoma (one 23-mm nodule in segment II). Both radiologists detected lesion and correctly assigned MRI tumor stage of T2. Asterisk indicates ascites. Superparamagnetic iron oxide-enhanced 2D SPGR transverse MR images obtained before administration of gadolinium at TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image at TE of 90 milliseconds (H) depict nodule (arrows) owing to high signal intensity. Image quality is limited by patient's obesity and marked ascites (asterisks).

 

Figure 18
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Fig. 5F —53-year-old woman with pathologic tumor stage T2 hypovascular hepatocellular carcinoma (one 23-mm nodule in segment II). Both radiologists detected lesion and correctly assigned MRI tumor stage of T2. Asterisk indicates ascites. Superparamagnetic iron oxide-enhanced 2D SPGR transverse MR images obtained before administration of gadolinium at TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image at TE of 90 milliseconds (H) depict nodule (arrows) owing to high signal intensity. Image quality is limited by patient's obesity and marked ascites (asterisks).

 

Figure 19
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Fig. 5G —53-year-old woman with pathologic tumor stage T2 hypovascular hepatocellular carcinoma (one 23-mm nodule in segment II). Both radiologists detected lesion and correctly assigned MRI tumor stage of T2. Asterisk indicates ascites. Superparamagnetic iron oxide-enhanced 2D SPGR transverse MR images obtained before administration of gadolinium at TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image at TE of 90 milliseconds (H) depict nodule (arrows) owing to high signal intensity. Image quality is limited by patient's obesity and marked ascites (asterisks).

 

Figure 20
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Fig. 5H —53-year-old woman with pathologic tumor stage T2 hypovascular hepatocellular carcinoma (one 23-mm nodule in segment II). Both radiologists detected lesion and correctly assigned MRI tumor stage of T2. Asterisk indicates ascites. Superparamagnetic iron oxide-enhanced 2D SPGR transverse MR images obtained before administration of gadolinium at TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image at TE of 90 milliseconds (H) depict nodule (arrows) owing to high signal intensity. Image quality is limited by patient's obesity and marked ascites (asterisks).

 

Figure 21
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Fig. 6A —54-year-old man with cirrhosis and false-positive lesion report. Radiologists reached different decisions on final interpretation. One radiologist scored nodule benign; one radiologist scored nodule malignant. Pathology report mentioned only regenerative nodules in liver segment, and no atypical nodules were found. Malignant interpretation by one radiologist was classified as false-positive lesion report. Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) image before gadolinium administration shows 9-mm nodule (arrow) in segment II has higher signal intensity than liver.

 

Figure 22
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Fig. 6B —54-year-old man with cirrhosis and false-positive lesion report. Radiologists reached different decisions on final interpretation. One radiologist scored nodule benign; one radiologist scored nodule malignant. Pathology report mentioned only regenerative nodules in liver segment, and no atypical nodules were found. Malignant interpretation by one radiologist was classified as false-positive lesion report. Dynamic 3D T1-weighted transverse fat-saturated SPGR images in hepatic arterial phase (B), portal venous phase (C), and equilibrium phase (D) after administration of gadolinium show nodule (arrows) does not become enhanced in arterial phase (B) but washes out relative to liver on delayed images (C and D).

 

Figure 23
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Fig. 6C —54-year-old man with cirrhosis and false-positive lesion report. Radiologists reached different decisions on final interpretation. One radiologist scored nodule benign; one radiologist scored nodule malignant. Pathology report mentioned only regenerative nodules in liver segment, and no atypical nodules were found. Malignant interpretation by one radiologist was classified as false-positive lesion report. Dynamic 3D T1-weighted transverse fat-saturated SPGR images in hepatic arterial phase (B), portal venous phase (C), and equilibrium phase (D) after administration of gadolinium show nodule (arrows) does not become enhanced in arterial phase (B) but washes out relative to liver on delayed images (C and D).

 

Figure 24
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Fig. 6D —54-year-old man with cirrhosis and false-positive lesion report. Radiologists reached different decisions on final interpretation. One radiologist scored nodule benign; one radiologist scored nodule malignant. Pathology report mentioned only regenerative nodules in liver segment, and no atypical nodules were found. Malignant interpretation by one radiologist was classified as false-positive lesion report. Dynamic 3D T1-weighted transverse fat-saturated SPGR images in hepatic arterial phase (B), portal venous phase (C), and equilibrium phase (D) after administration of gadolinium show nodule (arrows) does not become enhanced in arterial phase (B) but washes out relative to liver on delayed images (C and D).

 

Figure 25
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Fig. 6E —54-year-old man with cirrhosis and false-positive lesion report. Radiologists reached different decisions on final interpretation. One radiologist scored nodule benign; one radiologist scored nodule malignant. Pathology report mentioned only regenerative nodules in liver segment, and no atypical nodules were found. Malignant interpretation by one radiologist was classified as false-positive lesion report. Superparamagnetic iron oxide-enhanced 2D SPGR transverse MR images obtained before administration of gadolinium with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image with TE of 90 milliseconds (H) show nodule (arrows) with low signal intensity relative to liver as TE increases, suggesting elevated phagocytic function.

 

Figure 26
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Fig. 6F —54-year-old man with cirrhosis and false-positive lesion report. Radiologists reached different decisions on final interpretation. One radiologist scored nodule benign; one radiologist scored nodule malignant. Pathology report mentioned only regenerative nodules in liver segment, and no atypical nodules were found. Malignant interpretation by one radiologist was classified as false-positive lesion report. Superparamagnetic iron oxide-enhanced 2D SPGR transverse MR images obtained before administration of gadolinium with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image with TE of 90 milliseconds (H) show nodule (arrows) with low signal intensity relative to liver as TE increases, suggesting elevated phagocytic function.

 

Figure 27
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Fig. 6G —54-year-old man with cirrhosis and false-positive lesion report. Radiologists reached different decisions on final interpretation. One radiologist scored nodule benign; one radiologist scored nodule malignant. Pathology report mentioned only regenerative nodules in liver segment, and no atypical nodules were found. Malignant interpretation by one radiologist was classified as false-positive lesion report. Superparamagnetic iron oxide-enhanced 2D SPGR transverse MR images obtained before administration of gadolinium with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image with TE of 90 milliseconds (H) show nodule (arrows) with low signal intensity relative to liver as TE increases, suggesting elevated phagocytic function.

 

Figure 28
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Fig. 6H —54-year-old man with cirrhosis and false-positive lesion report. Radiologists reached different decisions on final interpretation. One radiologist scored nodule benign; one radiologist scored nodule malignant. Pathology report mentioned only regenerative nodules in liver segment, and no atypical nodules were found. Malignant interpretation by one radiologist was classified as false-positive lesion report. Superparamagnetic iron oxide-enhanced 2D SPGR transverse MR images obtained before administration of gadolinium with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echo-train spin-echo image with TE of 90 milliseconds (H) show nodule (arrows) with low signal intensity relative to liver as TE increases, suggesting elevated phagocytic function.

 

Figure 29
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Fig. 7A —49-year-old man with pathologic tumor stage T2 disease (two nodules measuring 8 [not shown] and 15 mm [arrows]) and false-negative lesion report. One radiologist detected hepatocellular carcinoma on superparamagnetic iron oxide (SPIO)-enhanced images and correctly assigned stage T2; other radiologist did not detect lesion on any images (error of observation). Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) images before gadolinium administration (A) and during hepatic arterial (B), portal venous (C), and equilibrium (D) phases after administration of gadolinium show poor visibility of nodules. In B, 15-mm nodule (arrow) in segment VI has ill-defined gadolinium enhancement.

 

Figure 30
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Fig. 7B —49-year-old man with pathologic tumor stage T2 disease (two nodules measuring 8 [not shown] and 15 mm [arrows]) and false-negative lesion report. One radiologist detected hepatocellular carcinoma on superparamagnetic iron oxide (SPIO)-enhanced images and correctly assigned stage T2; other radiologist did not detect lesion on any images (error of observation). Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) images before gadolinium administration (A) and during hepatic arterial (B), portal venous (C), and equilibrium (D) phases after administration of gadolinium show poor visibility of nodules. In B, 15-mm nodule (arrow) in segment VI has ill-defined gadolinium enhancement.

 

Figure 31
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Fig. 7C —49-year-old man with pathologic tumor stage T2 disease (two nodules measuring 8 [not shown] and 15 mm [arrows]) and false-negative lesion report. One radiologist detected hepatocellular carcinoma on superparamagnetic iron oxide (SPIO)-enhanced images and correctly assigned stage T2; other radiologist did not detect lesion on any images (error of observation). Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) images before gadolinium administration (A) and during hepatic arterial (B), portal venous (C), and equilibrium (D) phases after administration of gadolinium show poor visibility of nodules. In B, 15-mm nodule (arrow) in segment VI has ill-defined gadolinium enhancement.

 

Figure 32
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Fig. 7D —49-year-old man with pathologic tumor stage T2 disease (two nodules measuring 8 [not shown] and 15 mm [arrows]) and false-negative lesion report. One radiologist detected hepatocellular carcinoma on superparamagnetic iron oxide (SPIO)-enhanced images and correctly assigned stage T2; other radiologist did not detect lesion on any images (error of observation). Dynamic 3D T1-weighted transverse fat-saturated spoiled gradient-recalled echo (SPGR) images before gadolinium administration (A) and during hepatic arterial (B), portal venous (C), and equilibrium (D) phases after administration of gadolinium show poor visibility of nodules. In B, 15-mm nodule (arrow) in segment VI has ill-defined gadolinium enhancement.

 

Figure 33
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Fig. 7E —49-year-old man with pathologic tumor stage T2 disease (two nodules measuring 8 [not shown] and 15 mm [arrows]) and false-negative lesion report. One radiologist detected hepatocellular carcinoma on superparamagnetic iron oxide (SPIO)-enhanced images and correctly assigned stage T2; other radiologist did not detect lesion on any images (error of observation). SPIO-enhanced 2D SPGR transverse MR images with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echotrain spin-echo image with TE of 90 milliseconds (H) show hepatocellular carcinoma (arrows) visible as sharply circumscribed area of high signal intensity.

 

Figure 34
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Fig. 7F —49-year-old man with pathologic tumor stage T2 disease (two nodules measuring 8 [not shown] and 15 mm [arrows]) and false-negative lesion report. One radiologist detected hepatocellular carcinoma on superparamagnetic iron oxide (SPIO)-enhanced images and correctly assigned stage T2; other radiologist did not detect lesion on any images (error of observation). SPIO-enhanced 2D SPGR transverse MR images with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echotrain spin-echo image with TE of 90 milliseconds (H) show hepatocellular carcinoma (arrows) visible as sharply circumscribed area of high signal intensity.

 

Figure 35
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Fig. 7G —49-year-old man with pathologic tumor stage T2 disease (two nodules measuring 8 [not shown] and 15 mm [arrows]) and false-negative lesion report. One radiologist detected hepatocellular carcinoma on superparamagnetic iron oxide (SPIO)-enhanced images and correctly assigned stage T2; other radiologist did not detect lesion on any images (error of observation). SPIO-enhanced 2D SPGR transverse MR images with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echotrain spin-echo image with TE of 90 milliseconds (H) show hepatocellular carcinoma (arrows) visible as sharply circumscribed area of high signal intensity.

 

Figure 36
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Fig. 7H —49-year-old man with pathologic tumor stage T2 disease (two nodules measuring 8 [not shown] and 15 mm [arrows]) and false-negative lesion report. One radiologist detected hepatocellular carcinoma on superparamagnetic iron oxide (SPIO)-enhanced images and correctly assigned stage T2; other radiologist did not detect lesion on any images (error of observation). SPIO-enhanced 2D SPGR transverse MR images with TE of 2.6 milliseconds (E), 4.8 milliseconds (F), and 6.6 milliseconds (T2*-weighted) (G) and T2-weighted 2D echotrain spin-echo image with TE of 90 milliseconds (H) show hepatocellular carcinoma (arrows) visible as sharply circumscribed area of high signal intensity.

 

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