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Background: Diffusion-weighted (DW) imaging is commonly used to distinguish between benign and malignant liver lesions., Purpose: To prospectively evaluate the true molecular-diffusion coefficient (D), perfusion-related diffusion coefficient (D*), perfusion fraction (f), and ADC of focal hepatic lesions using a free-breathing intravoxel incoherent motion (IVIM) DW sequence, and to determine if these parameters are useful for characterizing focal hepatic lesions., Material and Methods: One hundred and twenty hepatic lesions (34 metastases, 32 hepatocellular carcinoma [HCC], 33 hemangiomas, and 21 liver cysts) in 74 patients were examined. Mean D, D*, f, and ADC values of hepatic lesions were compared among pathologies. ROC curve analyses were performed to assess the performances of D, D*, f, and ADC values for the characterization of liver lesions as benign or malignant., Results: The mean D and ADC values of benign lesions were greater than those of malignant lesions (P < 0.001). Although the mean D and ADC values of liver cysts were greater than those of hemangiomas (P < 0.001), and these values were not significantly different between metastases and HCCs (P = 0.99). Area under the ROC curve for ADC values (0.98) was significantly greater (P = 0.048) than that for D values (0.96) for the differentiation of benign and malignant lesions. Sensitivity and specificity for the detection of malignant lesion were 89% and 98%, respectively, when an ADC cut-off value of 1.40 was applied., Conclusion: D and ADC values have more potential for characterizing focal hepatic lesions than D* or f values, and for the differentiation of malignancy and benignity., (© The Foundation Acta Radiologica 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Objective: The purpose of this article is to prospectively evaluate the optimal scan delay for gadoxetate disodium-enhanced hepatic arterial phase MRI of hypervascular hepatocellular carcinoma (HCC) using MR fluoroscopic triggering and a slow-injection technique., Subjects and Methods: Sixty-three patients (37 men and 26 women; age range, 33-92 years; mean age, 68.2 years) underwent gadoxetate disodium-enhanced MRI; there were 33 hypervascular HCCs (size range, 8-57 mm; mean size, 19.8 mm) in 19 patients. The time from the start of contrast agent injection to its arrival in the abdominal aorta (time to arrival) and the time from contrast agent arrival to peak enhancement (time to peak) were determined using MR fluoroscopy using IV slow injection at 1 mL/s of contrast material and a saline chaser. All patients underwent four-phase whole-liver imaging with a 3D keyhole gradient-echo sequence during a single breath-hold immediately after confirmation of aortic peak enhancement. Delays from peak aortic enhancement to k-space filling were 5-9, 10-14, 15-19, and 20-28 seconds, respectively, in the four phases. Time to arrival, time to peak, and HCC-to-liver contrast were evaluated., Results: The time to arrival (range, 11-24 seconds; mean, 16.2 seconds) and the time to peak (range, 3-10 seconds; mean, 6.8 seconds) showed considerable variation among patients. HCC-to-liver contrast peaked at the first phase in 58% of cases, at the second phase in 42% of cases, and at the third and fourth phases in 0% of cases. Mean HCC-to-liver contrast in the first and second phases was significantly higher than that in the third and fourth phases (p<0.01)., Conclusion: Optimal scan delays for imaging hypervascular HCCs with gadoxetate disodium-enhanced hepatic arterial phase MRI was 7-12 seconds after the peak aortic enhancement using a slow-injection protocol.

Objective: The purpose of our study was to determine whether gadoxetate disodium-enhanced MRI improves the detection of locally recurrent hepatocellular carcinoma (HCC) after radiofrequency ablation therapy., Materials and Methods: Forty-two consecutive patients (26 men and 16 women; mean age, 70.9 years) who had undergone radiofrequency ablation therapy for HCC were examined by gadoxetate disodium-enhanced MRI. Three independent radiologists reviewed two sets of MR images separately. Set 1 contained unenhanced T1-weighted, T2-weighted, and contrast-enhanced extracellular phase images, and set 2 contained unenhanced T1-weighted, T2-weighted, and contrast-enhanced extracellular and hepatocyte phase images. Diagnostic accuracies were determined by receiver operating characteristic (ROC) curve analysis., Results: Of the 61 ablated lesions included, 10 developed local recurrence and 51 did not. Sensitivity (60-80% and 70-80% for sets 1 and 2, respectively), specificity (90-98% and 92-100%), and accuracy (87-95% and 89-97%) were not improved by adding hepatocyte phase images. Rather, mean area under the ROC curve (AUC) significantly decreased from 0.94 for set 1 to 0.82 for set 2 (p = 0.046), and the AUC of the radiologist with the least experience significantly decreased from 0.91 to 0.75 (p = 0.037)., Conclusion: For gadoxetate disodium-enhanced MRI, the detection of local recurrence of HCC after radiofrequency ablation therapy was not found to be improved by including hepatocyte phase images. Furthermore, detection may be further impaired when a less-experienced radiologist interprets the images.

Purpose: To retrospectively assess imaging features that help differentiate early-enhancing non-tumorous (EN) hepatic lesions from hepatocellular carcinomas (HCCs) on gadoxetate disodium-enhanced MR imaging., Materials and Methods: Our institutional review board approved this retrospective study. We reviewed the studies of 158 patients (92 men and 65 women; age range: 29-91; mean age: 65.6 years) with chronic liver damage, who underwent gadoxetate disodium-enhanced MR imaging at 3T MR scanner. Hypervascular lesions identified during the hepatic artery phase were selected for a study cohort. The location, shape, size (maximum diameter and maximum area), and contrast enhancement signal intensity characteristics of the lesions were evaluated, then compared between the EN and HCC lesions., Results: A total of 65 EN lesions (range: 3-60mm, mean: 13.6 ± 10.6 mm) from 35 patients and 33 HCCs (range: 9-61 mm, mean: 19.3 ± 12.6 mm) from 20 patients were identified. Lesions were more frequently round or oval in shape for HCCs (n=29; 88%) than ENs (n=26; 40%) (P<0.01). Unexpectedly, some ENs (n=12; 18%) showed hypointensity on hepatocyte-phase, and 6 (50%) of them were T2 hyperintense. For lesions smaller than 2 cm (9 ENs and 21 HCCs) on hepatic arterial-phase images, the mean area of hypointensity in hepatocyte-phase (54.2 ± 33.1 mm(2)) was significantly smaller than those of the corresponding hyperintensity in hepatic arterial-phase (97.1 ± 42.0 mm(2)) for EN lesions (P=0.019), whereas no significant difference in area was found for HCCs., Conclusion: EN lesions may occasionally present with hypointensity during the hepatocyte-phase; presenting a diagnostic dilemma. In this situation, EN lesions may be differentiated from HCCs when a hypointense area in hepatocyte-phase is smaller than the corresponding hypervascular area in hepatic-arterial phase., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: The purpose of this study was to prospectively determine the optimal acquisition delay for imaging of hypervascular hepatocellular carcinoma with multiphasic dynamic contrast-enhanced MRI., Subjects and Methods: One hundred twenty patients with chronic hepatic disease underwent three-phase dynamic contrast-enhanced MRI of the liver, which revealed 49 hypervascular hepatocellular carcinomas. Abdominal aortic contrast arrival time was determined with test bolus imaging. Patients were assigned to one of the following four groups according to acquisition delay determined from abdominal aortic contrast arrival time to the middle of the k-space for the early, late hepatic arterial, and portal venous phases: 0, 12, and 49 seconds (group 1); 3, 15, and 52 seconds (group 2); 6, 18, and 55 seconds (group 3); and 9, 21, and 58 seconds (group 4). Each phase of imaging took 12 seconds. Contrast enhancement in the abdominal aorta, portal vein, hepatic parenchyma, and hepatocellular carcinoma was evaluated. Peritumoral sinusoidal enhancement (i.e., coronal enhancement) also was assessed., Results: Intense enhancement of hepatocellular carcinoma with little background parenchymal enhancement occurred at 9-12 seconds (p < 0.05) after arrival of contrast material in the abdominal aorta. Hepatocellular carcinoma-to-liver contrast began to decline at 15 seconds and decreased to less than zero at 49 seconds. The conspicuity of coronal enhancement was greater 21 seconds after contrast administration than in earlier phases., Conclusion: With the injection protocol used in this study, optimal acquisition delay-determined from abdominal aortic contrast arrival time to the middle of the k-space acquisition-for imaging of hypervascular hepatocellular carcinoma was 9-12, 21 or more, and 49 seconds for the early, late hepatic arterial, and portal venous phases.

Purpose: The aim of this study was to evaluate the clinical capability of three-dimensional (3D) perfusion imaging of hepatocellular carcinoma (HCC) by performing dynamic scanning using a 256-slice multidetector-row CT (MDCT) scanner., Materials and Methods: Two patients with HCC were examined in this study. They were scheduled to undergo transcatheter arterial infusion therapy using an arterial infusion reservoir system. The CT system used was a newly developed prototype scanner of 256-slice MDCT. Dynamic CT scanning was performed with intraarterial injection via the reservoir route, and perfusion analysis was done based on the 3D data., Results: The blood flow volume per unit volume in the tumors was significantly increased compared with that in normal hepatic parenchyma. Using a 3D workstation, 3D perfusion images could be displayed by fusing CT images with perfusion images about blood flow volume., Conclusion: Three-dimensional perfusion images, which enable 3D evaluation of perfusion in HCCs, can be generated using 256-slice MDCT.

Purpose: To evaluate the detectability of local hepatocellular carcinoma (HCC) recurrence after transcatheter arterial chemoembolization (TACE) by diffusion-weighted MR imaging in correlation with those of gadolinium-enhanced MR imaging., Materials and Methods: Respiratory-triggered diffusion-weighted MR images (b factor, 500 s/mm(2); number of averaging, six were obtained in 25 patients with 39 HCCs. Two independent radiologists evaluated diffusion-weighted MR images, gadolinium-enhanced MR images after TACE, and assigned confidence levels for postoperative HCC recurrence. Apparent diffusion coefficients (ADCs) in HCCs were also measured. Sensitivities and specificities were compared using an extension of the McNemar test. Observer performance was also determined by ROC curve analysis., Results: Local recurrences in 14 HCCs and complete tumor necrosis in 25 HCCs after TACE were determined. Sensitivity for the detection of local HCC recurrence was higher on gadolinium-enhanced MR imaging (82%) than on diffusion-weighted MR imaging (60.7%) for the two readers in combination and separately (P < 0.05). Specificities were comparably high for both sequences. Az values were higher for gadolinium-enhanced MR images (0.92) than for diffusion-weighted MR images (0.74) for readers in combination and separately (P < 0.05). Mean ADC values showed an increase after TACE (P < 0.001)., Conclusion: Diffusion-weighted MR imaging was not found to be a reliable predictor of local HCC recurrence after TACE as compared with gadolinium-enhanced MR imaging., ((c) 2008 Wiley-Liss, Inc.)

Objective: The purpose of our study was to evaluate the clinical feasibility and usefulness of a 2D spoiled gradient-recalled echo MR sequence with serial switching of reversed centric and centric k-space reordering for high-spatial-resolution gadolinium-enhanced double hepatic arterial phase (HAP) MRI of the liver., Subjects and Methods: MR images (frequency, 512; phase encoding without interpolation, 224; 6-mm thickness with 1-mm gap; 30 slices per 18 seconds) were obtained with multiphase imaging in which central k-space line data were filled 10, 21, 49, and 181 seconds after arrival of contrast medium in the abdominal aorta for the early HAP (reversed centric reordering, center of k-space lines acquired at end of acquisition), late HAP (centric reordering, center of k-space lines at beginning of acquisition), portal venous phase (centric reordering), and equilibrium phase (centric reordering), respectively, in 102 consecutive patients with suspected liver disease, including 48 untreated hepatocellular carcinomas (HCCs) in 35 patients. Images were quantitatively assessed for degree of contrast enhancement in the abdominal aorta, spleen, portal trunk, liver parenchyma, hepatic veins, and HCCs. Images were qualitatively assessed for the effectiveness of contrast enhancement in each phase and for degree of image degradation due to artifacts., Results: Enhancement of the abdominal aorta peaked in the early HAP, of the portal trunk in the late HAP, and of the hepatic parenchyma and veins in the portal venous phase. Mean HCC-to-liver contrast peaked in the early HAP and turned to a negative value in the portal venous and equilibrium phases. Sufficient image quality was achieved in 99 (97%) of the patients. One of the other three patients had motion artifacts due to body motion, and the other two had unsatisfactory respiratory suspension. Scan timing for early and late HAP was optimal in 74 (73%) of the patients, for late HAP lagged in 20 (20%), for early HAP was premature in six (6%), and for early HAP lagged in five (5%) of the patients., Conclusion: We confirmed the feasibility and usefulness of a 2D gadolinium-enhanced double HAP spoiled gradient-recalled echo sequence incorporating serial switching of reversed centric and centric k-space reordering. This method has the potential for use in high-spatial-resolution double HAP MRI for the diagnosis of hypervascular HCC.

Objective: The purpose of our study was to determine the optimal scan delays required for hepatic arterial and portal venous phase imaging and for the detection of hypervascular hepatocellular carcinomas (HCCs) in contrast-enhanced MDCT of the liver using a bolus-tracking program., Subjects and Methods: CT images (2.5-mm collimation, 5-mm thickness with no intersectional gap) detected an increase in the CT value of 50 H in the lower thoracic aorta. The images were obtained after an IV bolus injection of 2 mL/kg of nonionic iodine contrast material (300 mg I/mL) at 4 mL/s in 171 patients, who were prospectively randomized into three groups with scans commencing at 5, 20, and 45 seconds; 10, 25, and 50 seconds; and 15, 30, and 55 seconds for the first (acquisition time: 4.3 seconds), second (4.3 seconds), and third (9.1 seconds) phases, respectively, after a bolus-tracking program. CT values of the aorta, spleen, proximal portal veins, liver parenchyma, and hepatic veins were measured. Increases in CT values from unenhanced to contrast-enhanced CT were assessed using a contrast enhancement index (CEI). Spleen-to-liver and HCC-to-liver contrasts were also assessed. A qualitative degree of contrast enhancement in each organ was prospectively assessed by two independent radiologists., Results: At 10-15 seconds, the CEI of the aorta reached 300-336 H and that of the spleen reached 97-108 H without significant enhancement of liver parenchyma (15-25 H). The CEI of the proximal portal veins moderately increased (75-104 H) at 10-15 seconds, but no significant enhancement of hepatic veins was observed (24-51 H). The CEI of liver parenchyma peaked (59-63 H) at 45-55 seconds, when the CEIs of the aorta (117-125 H) and spleen (73-82 H) decreased. Spleen-to-liver contrast (81-84 H) was highest at 10-20 seconds and HCC-to-liver contrast (39-44 H) was highest at 10-15 seconds. The qualitative results correlated well with quantitative results., Conclusion: The optimal scan delays for hepatic arterial and portal venous phases after the bolus-tracking program detected threshold enhancement by 50 H in the lower thoracic aorta for the detection of hypervascular HCCs were 10-15 and 45-55 seconds, respectively.

Purpose: To elucidate the morphologic appearance of small non-tumorous arterioportal (AP) shunts mimicking hepatocellular carcinoma on helical computed tomography (CT), their associated outcomes, and their relationship with alpha-fetoprotein levels in patients with chronic liver disease., Materials and Methods: Ten patients with multiple AP shunts on dynamic helical CT were evaluated. A non-tumorous AP shunt was defined as no increase or spontaneous regression in size on follow-up CT scans. The number and shape of shunts more than 5 mm in diameter were studied on a segment-by-segment basis on the initial CT scan, and compared with those on follow-up CT scans. Alpha-fetoprotein levels were measured at the same time as CT scanning was performed., Results: Ten patients with 86 AP shunts (range 0.5-3.8 cm; mean 1.2 cm) underwent arterial, portal and delayed phase imaging of the entire liver. The AP shunts were geographic (44%), round (33%) or wedge-like (23%) in shape. All shunts changed from high- to iso-attenuation on the delayed phase CT. A follow-up CT (mean 73 days) revealed spontaneous disappearance in all but three (97%) of the 86 AP shunts. Furthermore, 16 new shunts appeared in different segments from the primary ones in four patients. The rapid elevation of alpha-fetoprotein levels to 5-10-fold higher than the baseline level was recognized at the same time as the initial appearance of AP shunts in three patients (30%). Further follow-up CT scans detected solitary hepatocellular carcinomas in four patients at a mean 1283 days after the initial CT. The location of the hepatocellular carcinomas was quite different from those of the initially recognized AP shunts., Conclusions: Non-tumorous AP shunts varied in CT appearance and demonstrated iso-attenuation in the delayed phase, most of which disappeared within 4 months. For these multiple small stains in chronic liver disease, periodic follow-up CT is recommended rather than alternative invasive interventions, even though there was an association with rapid elevation of alpha-fetoprotein levels.

Objective: To determine the optimal scan delay required for fixed duration contrast injection in contrast-enhanced biphasic multidetector-row CT for the liver and the detection of hypervascular hepatocellular carcinoma (HCC)., Methods: CT images (2.5-mm collimation, 5-mm thickness with no intersectional gap) were obtained after an intravenous bolus injection of 2 mL/kg of nonionic iodine contrast material (300 mg I/mL) for a fixed 30-second injection in 206 patients, who were prospectively randomized into four groups, for which scans were initiated at -5, 15, and 35 seconds; at 0, 20, and 40 seconds; at 5, 25, and 45 seconds; or at 10, 30, and 50 seconds for the first (acquisition time: 4.3 seconds), second (4.3 seconds), and third (9.1 seconds) phases, respectively, after the completion of contrast injection. Mean CT values (HU) of the abdominal aorta, spleen, main portal veins, liver parenchyma, and hepatic veins were measured. Increases in CT values between pre- and post-contrast CTs (DeltaHU) for the organs, and spleen-to-liver and HCC-to-liver contrast differences (deltaHU) were assessed., Results: Abdominal aorta reached 273-301 DeltaHU at -5 to 10 seconds with a peak (301 DeltaHU) at 5 seconds. Spleen peaked (115 DeltaHU) at 10 seconds. Liver parenchyma were enhanced weakly (11-34 DeltaHU) at -5 to 10 seconds, exceeded 50 DeltaHU at 20 seconds, peaked (61 DeltaHU) at 30 seconds, and then plateaued (54-58 DeltaHU) at 35-50 seconds. Hepatic veins were enhanced weakly (14-37 DeltaHU) at -5 to 10 seconds, and reached 67 DeltaHU at 15 seconds. Spleen-to-liver (65-69 deltaHU) and HCC-to-liver (31-34 deltaHU) contrast differences were highest at 5-10 seconds. Qualitative results corresponded well with quantitative results., Conclusions: For the detection of hypervascular HCCs, the optimal scan delay after a 30-second contrast injection of the hepatic arterial phase, was found to range from 5 to 10 seconds, and that of the portal venous phase was 35 seconds or somewhat longer.

Objective: The purpose of our study was to assess the correlation between the quantitative and qualitative imaging findings on unenhanced and gadolinium-enhanced MR images and the intensity of vascular endothelial growth factor (VEGF) expression in hepatocellular carcinomas and in the surrounding nontumorous liver., Materials and Methods: The intensities of VEGF expression in hepatocellular carcinoma and in the surrounding liver by Western blot analysis were converted to VEGF expression indexes (VEGF(IND)) in 22 surgical specimens ranging in size from 14 to 126 mm (mean, 47.6 +/- 29.5 mm) that were resected in 22 patients (17 men and five women; age range, 41-85 years [mean, 64 years]) between April 2000 and October 2002. MR images were retrospectively evaluated to determine contrast-to-noise ratios (CNRs), signal intensity SD ratios, and phase-shift indexes. Signal intensity characteristics of hepatocellular carcinomas were reviewed independently by two experienced radiologists who were unaware of the pathologic diagnosis or the results of immunoblotting. CNRs, SD ratios, and phase-shift indexes were correlated with VEGF(IND) using a simple regression test, and signal intensity characteristics were correlated with VEGF(IND) using the Spearman's rank correlation test., Results: On opposed-phase T1-weighted spoiled gradient-recalled echo (GRE) images, CNRs correlated inversely with the VEGF(IND) of hepatocellular carcinomas (r = -0.46, p = 0.038). CNRs on T2-weighted fast spin-echo images correlated directly with the VEGF(IND) of hepatocellular carcinomas (r = 0.49, p = 0.025), and on gadolinium-enhanced hepatic arterial phase GRE images marginally and inversely correlated with VEGF(IND) (r = -0.39, p = 0.081). On T2-weighted fast spin-echo images, SD ratios correlated directly with the VEGF(IND) of hepatocellular carcinomas (r = 0.44, p = 0.044). No correlation was found between phase-shift indexes and VEGF expression. The qualitatively assessed signal intensity heterogeneities of hepatocellular carcinomas correlated directly with the VEGF(IND) of hepatocellular carcinomas on opposed-phase T1-weighted GRE, T2-weighted fast spin-echo, hepatic arterial phase GRE, and equilibrium phase GRE images., Conclusion: Our results indicate that the signal intensity and heterogeneity of hepatocellular carcinomas on MR images correlate with the degree of VEGF expression in hepatocellular carcinomas.

The purpose of our study was to determine whether or not the addition of T2-weighted fast spin-echo (SE) imaging to gadolinium-enhanced spoiled gradient-recalled-echo (GRE) imaging improves the observer performance in the preoperative detection of malignant hepatic tumors. Gadolinium-enhanced GRE and fat-suppressed T2-weighted fast SE images obtained in 49 patients with 82 surgically confirmed malignant hepatic tumors (40 hepatocellular carcinomas and 42 metastases) were retrospectively reviewed by three independent off-site observers. In the random review of images, gadolinium-enhanced GRE images were reviewed first; thereafter, T2-weighted fast SE images were added for combined review. Observer performance was evaluated with the McNemar's test and receiver operating characteristic curve analysis. For gadolinium-enhanced GRE images alone vs. combined images, sensitivities for detection were 78% vs. 79% for hepatocellular carcinomas (P>.05), 67% vs. 71% for metastases (P<.05) and 72% vs. 75% for tumors overall (P<.05), respectively. The Az values were 0.892 vs. 0.889 in hepatocellular carcinomas (P>.05), 0.797 vs. 0.828 in metastases (P<.05) and 0.839 vs. 0.846 in tumors overall (P>.05), respectively. Our results showed that the addition of T2-weighted fast SE imaging to gadolinium-enhanced GRE imaging improved the observer performance in the detection of metastases.

A 65-year-old man with multiple hepatocellular carcinomas in the liver with type C viral hepatitis had a solitary mediastinal lymph node metastasis in the right paratracheal to tracheobronchial region. Surgical resection for the mediastinal metastasis was undertaken based on magnetic resonance (MR) imaging findings, suggesting its radicality. We assess the MR imaging findings and presumable pathways of lymphatic metastasis from the liver to mediastinal lymph nodes in this report.

Objective: The purpose of our study was to assess the correlation between the intensity and characteristics of contrast enhancement on angiographically assisted CT and the intensity of vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and in the surrounding nontumorous liver., Materials and Methods: The intensity of VEGF expression in HCC and in the surrounding liver was expressed as a VEGF expression index by Western blot analysis in 20 surgical specimens resected in 20 patients between March 2000 and August 2002. Findings on CT during arterial portography (n = 20) and CT hepatic arteriography (n = 17) were retrospectively evaluated to determine contrast enhancement indexes and the enhancement characteristics of HCCs and of the surrounding liver. Contrast enhancement indexes and VEGF expression indexes were correlated using a simple regression test, and enhancement characteristics and VEGF expression indexes were correlated using the Spearman's rank correlation test., Results: On CT hepatic arteriography, the contrast enhancement indexes of HCCs showed moderate inverse correlation with the VEGF expression indexes of HCCs (r = -0.57, p = 0.017) and high inverse correlation with the differences between the VEGF expression indexes of HCCs and those of livers (difference in the VEGF expression index, -0.80; p = 0.0001). The contrast enhancement index of the liver showed marginal moderate direct correlation with the VEGF expression index of the liver (0.44, p = 0.076) and high inverse correlation with the difference in the VEGF expression index (-0.71, p = 0.0013). On CT during arterial portography, the contrast enhancement indexes of HCCs showed moderate inverse correlation with the difference in the VEGF expression index (-0.51, p = 0.023). The qualitative degree of heterogeneity of hepatic artery enhancement in HCC on CT hepatic arteriography showed moderate direct correlation with the VEGF expression indexes of HCCs (0.55, p = 0.033) and high direct correlation with the difference in the VEGF expression indexes (0.73, p = 0.004)., Conclusion: Our results indicated that the intensity and heterogeneity of hepatic artery enhancement of HCCs on CT hepatic arteriography correlated with the degree of VEGF expression in HCCs.

Background/aims: This study examines the prognostic factors including radiological findings of hepatocellular carcinoma presenting with macroscopic portal vein tumor thrombus., Methodology: From September 1992 to December 2002, 107 patients with hepatocellular carcinoma and a macroscopic portal vein tumor thrombus were treated at the National Cancer Center Hospital East. Patients' characteristics and diagnostic findings of computed tomography, angiography and computed tomography angiography were analyzed to determine the factors significantly related to the patients' prognosis., Results: Enhanced portal vein tumor thrombus, main tumor occupying over 40% of the liver and distribution of tumors significantly affected survival. Cavernous transformation, thread and streak signs, arterio-portal shunt, extent of tumor thrombus, grade of venous invasion and tumor size did not affect survival. Clinical findings showed that Child-Pugh classification score over 7, etiology of hepatitis, total bilirubin over 2.2 mg/dL, prothrombin time under 50% and liver transaminases over 100 IU/L were poor prognostic factors. Multivariate analysis showed that AST over 100 IU/L, viral hepatitis and tumor occupying over 40% of the liver strongly affected the prognosis., Conclusions: Based on the present results, the most strongly affected prognostic factor was liver function as indicated by high level of transaminases. Various radiological findings did not affect survival. The elevation of transaminases seemed due to destruction of hepatocytes by growing tumor and circulatory disruption due to portal vein tumor thrombus. We concluded that radiological findings of hepatocellular carcinoma presenting with portal vein tumor thrombus indicated only intrahepatic status but not survival. First treatment for hepatocellular carcinoma presenting with portal vein tumor thrombus should be to improve the liver function. Treatment against hepatitis virus might be important and patients with AST over 100 IU/L and a tumor occupying over 40% should not undergo surgical resection.

Purpose: To perform comparison of gadolinium-enhanced and ferumoxides-enhanced magnetic resonance imaging (MRI) in the detection of nodule-in-nodule appearance of hepatocellular carcinomas (HCCs)., Materials and Methods: During a recent 45-month period, we had eight patients (five men and three women; age range, 63-84 years; mean, 71 years) with HCCs with nodule-in-nodule appearance who underwent gadolinium-enhanced MRI, ferumoxides-enhanced MRI, and computed tomography during arterial portography (CTAP) and computed tomography during hepatic arteriography (CTHA), combined and separately, within an interval of two weeks. Two blinded radiologists in consensus retrospectively evaluated three sets of sequences: unenhanced T1- and T2-weighted MR, gadolinium-enhanced MR, and ferumoxides-enhanced MR images in random order of patients and imaging sequences. The depiction degree of nodule-in-nodule appearance of HCC was evaluated in a semiquantitative fashion. The sensitivities of unenhanced T1- and T2-weighted, gadolinium-enhanced, and ferumoxides-enhanced MR images were compared with McNemar's test., Results: The eight HCCs with nodule-in-nodule appearance ranged in size from 16-26 mm (mean, 20.0 +/- 4.0 mm), and there existed nine internal HCC foci ranging in size from 5-14 mm (mean, 7.9 +/- 3.5 mm). On gadolinium-enhanced MR images, the nodule-in-nodule appearance of HCC was typically seen as hypervascular foci in an iso- or hypovascular area: the depiction degree of nodule-in-nodule appearance was distinct in two lesions, equivocal in three, and absent in three. On ferumoxides-enhanced MR images, it was typically seen as hyperintense foci in a hypointense area: the depiction degree was distinct in four, moderate in one, and absent in three. The sensitivities for detection of nodule-in-nodule appearance were 25%, 25%, and 63% on T1- and T2-weighted, gadolinium-enhanced, and ferumoxides-enhanced MR images, respectively, but there was no significant difference in sensitivity., Conclusion: Nodule-in-nodule appearance of HCCs can be seen on ferumoxides-enhanced MR images, in some cases more clearly than on gadolinium-enhanced MR images, particularly when the background nodule shows hyperintensity on precontrast T1-weighted images. Ferumoxides-enhanced MRI may be considered when development of malignant foci is suspected during routine examinations., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: To assess the frequency, imaging findings, and significance of early-enhancing nonneoplastic (EN) lesions with gadolinium-enhanced magnetic resonance imaging (MRI) of the liver following partial hepatectomy., Materials and Methods: We retrospectively reviewed MR images after partial hepatectomy in 30 patients. Postoperative MRI was performed in 1-12 months (mean, 3.7 months) after partial hepatectomy. We defined the EN lesion as a lesion that was ill defined; irregular, wedge shaped, or serpiginous; located along the liver edge; not visible on unenhanced MR images; did not appear hypointense on portal venous- or equilibrium-phase images; or a combination of those imaging findings., Results: A total of 39 EN lesions (size range, 5-60 mm; mean, 25.2 mm) in 19 patients and 17 recurrent tumors (size range, 5-50 mm; mean, 16.8 mm) in 10 patients newly appeared after partial hepatectomy. The EN lesions were diagnosed as pseudolesions by the second postoperative follow-up MRI in 17 patients or contrast-enhanced computed tomography (CT) in two. A total of 13 EN lesions (33%) were located along the liver edge and 20 (51%) were adjacent to the resected area. The shape was circular in 11 (28%), oval in three (8%), irregular in 11 (28%), wedge shaped in five (13%), and serpiginous in nine (23%). No EN lesion showed hypointensity on gadolinium-enhanced portal venous-phase or equilibrium-phase images. A total of 14 EN lesions (36%) showed slight hyperintensity on T2-weighted images. The confidence levels for malignancy probability assigned by blinded radiologists were lower with EN lesions than with recurrent tumors (P < 0.001)., Conclusion: EN lesions are frequently seen in MRI following partial hepatectomy, and occasionally are slightly hyperintense on T2-weighted images, mimicking malignant tumors. However, most EN lesions can be correctly diagnosed with MRI findings., (Copyright 2004 Wiley-Liss, Inc.)

Purpose: To determine whether chemical-shift-selective (CSS) fat suppression is necessary for ferumoxide-enhanced T2-weighted fast spin-echo (FSE) imaging in the detection of malignant hepatic tumors., Materials and Methods: Ferumoxide-enhanced magnetic resonance (MR) images obtained in 38 patients with surgically confirmed 61 malignant hepatic tumors (36 hepatocellular carcinomas (HCCs), 25 metastases) were retrospectively reviewed by three independent readers. Three sequences of MR images with CSS fat-suppressed T2-weighted FSE, non-fat-suppressed T2-weighted FSE, and T2*-weighted gradient-recalled-echo (GRE) sequences were randomly reviewed on a segment-by-segment basis in a blind fashion. Observer performance was tested using the McNemar's test and receiver-operating-characteristic (ROC) analysis for the clustered data. Lesion-to-liver contrast-to-noise ratio (C/N) was also assessed., Results: The mean C/N with the CSS fat-suppressed FSE sequence was highest in HCCs, metastases, and tumors overall. Sensitivity was highest with the CSS fat-suppressed FSE sequence in HCC, was highest with the non-fat-suppressed FSE sequence in metastases, and was comparable in tumors overall. Specificity was comparable between the sequences. The area under ROC curve (Az) value was greatest with the CSS fat-suppressed FSE sequence in HCCs, was greatest with the non-fat- suppressed FSE sequence in metastases, and was comparable in tumors overall. The sensitivities and Az values were lower with the GRE sequence than the FSE sequence., Conclusion: The CSS fat-suppressed FSE sequence was superior to the GRE sequence in the detection of HCCs, but the non-fat-suppressed FSE sequence was comparable to the GRE sequence. The non-fat-suppressed FSE sequence was superior to the CSS fat-suppressed FSE and GRE sequences in the detection of metastases. Optimal FSE imaging with CSS fat suppression or without aiming for the detection of HCCs or metastases, respectively, outperforms GRE imaging in ferumoxide-enhanced MRI., (Copyright 2004 Wiley-Liss, Inc.)

The purpose of our study was to assess whether respiratory-triggered multishot fast spin echo (MS-FSE) and breath-hold half-Fourier single-shot fast spin echo (SS-FSE) images, in addition to breath-hold T(2)*-weighted gradient recalled echo (GRE) images, increase observer performance in the detection of malignant hepatic tumors with ferumoxide-enhanced magnetic resonance (MR) imaging. Ferumoxide-enhanced MR images obtained from 48 patients with 83 malignant hepatic tumors were retrospectively reviewed by three independent off-site readers. In the first image review, GRE images alone were reviewed. Then, MS-FSE images were added for the first combination review. Finally, SS-FSE images were added for the second combination review. Observer performances were tested by McNemar's test and receiver-operating-characteristic analysis for the clustered data. Sensitivity for hepatocellular carcinomas, metastases, and malignant hepatic tumors overall was significantly (p < 0.05) higher with GRE and MS-FSE combined and GRE, MS-FSE and SS-FSE combined than with GRE alone. For metastases, the Az value was significantly (p < 0.05) higher with GRE and MS-FSE combined, and GRE, MS-FSE and SS-FSE combined than with GRE alone. We confirmed the incremental value of ferumoxide-enhanced MR imaging by obtaining MS-FSE and SS-FSE images in addition to GRE images in the detection of malignant hepatic tumors.

Objective: The purpose of our study was to compare the detectability of malignant hepatic tumors on ferumoxides-enhanced MRI using five gradient-recalled echo sequences at different TEs., Materials and Methods: Ferumoxides-enhanced MRIs obtained in 31 patients with 50 malignant hepatic tumors (33 hepatocellular carcinomas, 17 metastases) were reviewed retrospectively by three independent offsite radiologists. T1-weighted gradient-recalled echo images with TEs of 1.4 and 4.2 msec; T2*-weighted gradient-recalled echo images with TEs of 6, 8, and 10 msec; and T2-weighted fast spin-echo images of livers were randomly reviewed on a segment-by-segment basis. Observer performance was tested using the McNemar test and receiver operating characteristic analysis for the clustered data. Lesion-to-liver contrast-to-noise ratio was also assessed., Results: Mean lesion-to-liver contrast-to-noise ratios were negative and lower with gradient-recalled echo at 1.4 msec than with the other sequences. Sensitivity was higher (p < 0.05) with gradient-recalled echo at 6, 8, and 10 msec and fast spin-echo sequences (75-83%) than with gradient-recalled echo sequences at 1.4 and 4.2 msec (46-48%), and was higher (p < 0.05) with gradient-recalled echo sequence at 8 msec (83%) than with gradient-recalled echo at 6 msec and fast spin-echo sequences (75-78%). Specificity was comparably high with all sequences (95-98%). The area under the receiver operating characteristic curve (A(z)) was greater (p < 0.05) with gradient-recalled echo at 6, 8, and 10 msec and fast spin-echo sequences (A(z) = 0.91-0.93) than with gradient-recalled echo sequences at 1.4 and 4.2 msec (A(z) = 0.82-0.85)., Conclusion: In the detection of malignant hepatic tumors, gradient-recalled echo sequences at 8 msec showed the highest sensitivity and had an A(z) value and lesion-to-liver contrast-to-noise ratio comparable with values from gradient-recalled echo sequences at 6 and 10 msec and fast spin-echo sequences.

Purpose: To evaluate ferumoxide-enhanced MR imaging findings of hepatocellular carcinomas (HCCs) in correlation with the histologic tumor grades and the tumor vascularity evaluated by CT hepatic arteriography (CTHA) and CT during arterial portography (CTAP) combined., Materials and Methods: By searching the radiologic, surgical, and pathologic reports of our institution between January 1999 and February 2001, we identified 43 patients with 51 pathologically confirmed HCCs who underwent ferumoxide-enhanced MR imaging and combination CTHA and CTAP within two weeks. The HCCs consisted of 17 well-differentiated, 28 moderately differentiated, and six poorly differentiated tumors. The MR and CT were retrospectively reviewed by two radiologists in consensus for signal intensity on MR images and vascularity on CT. The Spearman's rank correlation coefficient was calculated to correlate the frequency of tumors with ferumoxide uptake with the histologic tumor grades and the tumor vascularity on CTHA and CTAP., Results: A total of 45 tumors (88%) did not take up ferumoxide, and thus showed distinct, homogeneous hyperintensity. Six tumors (12%) ranging 5-16 mm in size (mean, 11 mm) took up ferumoxide, and thus showed isointensity, mixed intensity, or hypointensity, including five of 17 (29%) well-differentiated tumors and one of 28 (4%) moderately differentiated tumors. Five of the six tumors (83%) showed hyper- or hypovascularity on CTHA or hypovascularity on CTAP. The frequency of tumors with ferumoxide uptake showed weak correlation with tumor grades (coefficient = 0.26, P < 0.01) and vascularity on CTHA (-0.35, P < 0.05) and CTAP (0.39, P < 0.01)., Conclusion: Although a small number of well-differentiated HCC take up ferumoxide and show iso-, mixed, or hypointensity, most such tumors show increased hepatic arterial or decreased portal venous perfusion. The present results suggest the limitation of reticuloendothelial contrast imaging, particularly in the diagnosis of small, well-differentiated HCC., (Copyright 2003 Wiley-Liss, Inc.)

Early hepatocellular carcinoma (HCC) as defined by the Liver Cancer Study Group of Japan would correspond to high-grade dysplastic nodules with small foci of HCC in the majority of cases, using the classification system proposed by the International Working Party. A large number of early HCCs were revealed to be hypo- or isovascular in the arterial phase of dynamic CT. Only 5% of the lesions evaluated were hypervascular, which contrasted with advanced small HCCs, of which 94% were hypervascular. CT arterial portography (CTAP) showed hypoattenuation in 66% of early HCCs and isoattenuation in 34%. CT hepatic arteriography (CTHA) demonstrated hypoattenuation in 55% of early HCC, isoattenuation in 30% and hyperattenuation in 15%. These findings suggest that most early HCCs receive equal or reduced blood supply from both portal and arterial flow compared with surrounding noncancerous parenchyma. In contrast, 97% of small HCCs are hypoattenuated on CTAP, and 93% are hyperattenuated on CTHA. For nodule-in-nodule type HCC (advanced HCC within early HCC), the CT attenuation of the central and peripheral portions revealed areas of isolated advanced HCC and isolated early HCC, respectively. Adenomatous hyperplasia (low-grade dysplastic nodules) was not readily differentiated using the various imaging modalities, mainly due to the smaller size of these lesions compared to early HCC and/or a portal and arterial blood supply very similar to that of the surrounding parenchyma. Hemodynamic changes in cirrhotic liver were similarly evaluated using CTAP and CTHA, and the treatment of early HCC is briefly discussed herein., (Copyright 2004 S. Karger AG, Basel)

We describe the magnetic resonance (MR) imaging findings of a small scirrhous hepatocellular carcinoma in a 74-year-old man. The initial MR imaging findings indicated that the tumor had a small central scar, which suggested the differential diagnoses of hepatocellular carcinoma, intrahepatic cholangiocarcinoma, and metastasis. A small scirrhous hepatocellular carcinoma may have a central scar and should be included in the differential diagnoses for small hepatic masses with a central scar., (Copyright 2002 Wiley-Liss, Inc.)

Aim: To study the clinicopathologic characteristics of hepatic nodular lesions with high attenuation (increased portal blood flow) compared with surrounding hepatic parenchyma on computed tomography (CT) during arterial portography (CTAP)., Methods: For six lesions found in six patients demonstrated as a high-attenuated mass by CTAP, CT during hepatic arteriography (CTHA; n = 3 patients), digital subtraction hepatic arteriography (n = 6) and conventional helical CT (n = 6) were evaluated retrospectively and compared with histopathologic findings (n = 4). Pathologic diagnosis was atypical adenomatous hyperplasia, nodule-in-nodule hepatocellular carcinoma (HCC) in one resected lesion each and overt HCC in two biopsied lesions. Two patients did not undergo any therapy and were followed up., Results: The average size of lesions was 2.2 cm (range 1.2-3.5 cm). The CTAP revealed high attenuation in all six lesions; entirely within the lesion (n = 4 lesions) or peripherally with a central low attenuation (n = 2). In contrast, CTHA showed low attenuated lesions; entirely within the mass (n = 2) or peripherally with a central high-attenuated spot (n = 1). Hepatic arteriogram revealed only two hypervascular lesions; entirely and partially in one each. In the arterial phase of helical CT, all but one lesion were iso- or hypo-attenuated. In two patients who were followed up to 39 and 55 months without therapy, neither tumor growth nor hemodynamic change of the lesion was recognized on CT., Conclusions: Even though the incidence of hepatic nodular lesions demonstrated as high attenuating on CTAP is low, all but one lesion in the current series showed iso- or hypo-attenuation on CTHA and/or helical CT, suggesting the hemodynamics are reciprocal between CTAP and CTHA. One exceptional lesion that showed high attenuation on both CTAP and conventional CT was pathologically advanced HCC. Based on the follow-up study of two untreated patients, this kind of lesion with high attenuation on CTAP seems to grow slowly., (Copyright 2002 Blackwell Publishing Asia Pty Ltd)

Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3-4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19-45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC., (Copyright 2002 S. Karger AG, Basel)