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Purpose: To assess the diagnostic abilities of diffusion-weighted imaging (DWI) with parallel imaging (PI-DWI) and that with Compressed SENSE (EPICS-DWI) for differentiating hepatic hemangiomas (HHs) and liver metastases (LMs)., Method: This prospective study included 30 participants with HH and/or LM who underwent PI-DWI and EPICS-DWI. Two radiologists assessed the DWI images and assigned confidence scores for hepatic lesions conspicuity using 4-point scale. One of the radiologists additionally calculated the contrast-to-noise ratio (CNR) and measured ADC value of the hepatic lesions. The conspicuity, CNR, and ADC values were compared between the two sequences. A receiver operating characteristic (ROC) analysis was performed to assess the diagnostic abilities of the two sequences for differentiating HHs and LMs., Results: The conspicuity of LMs was better in EPICS-DWI than in PI-DWI (P < .05 in both radiologists). The CNR of LMs was higher in EPICS-DWI than in PI-DWI (P = .008). No difference was found in the CNR of HHs (P = .52), ADC values for HHs (P = .79), and LMs (P = .29) between the two sequences. To differentiate between HHs and LMs, the cutoff ADC values were 1.38 × 10 -3 mm 2 /s in PI-DWI and 1.37 × 10 -3 mm 2 /s in EPICS-DWI. The area under the ROC curve (P = .86), sensitivity (P > .99), and specificity (P > .99) did not vary., Conclusions: The LMs were more visible in EPICS-DWI than in PI-DWI. However, the cutoff ADC values and diagnostic abilities for differentiating HHs and LMs were almost comparable between the two sequences., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: This study aims to compare the diagnostic values of mono-exponential, bi-exponential, and stretched exponential diffusion-weighted imaging (DWI) in differentiating hepatic hemangiomas and liver metastases., Method: This prospective study was approved by our institutional review board, and written informed consent was obtained from all patients. In this study, 244 patients with known or suspected liver disease underwent magnetic resonance imaging. Among them, 37 patients who had focal hepatic lesions with a maximum diameter of ≥10 mm were evaluated. Using home-built software, two radiologists measured the DWI parameters of hepatic lesions for the three models: the apparent diffusion coefficient (ADC) from a mono-exponential model; the true diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) from a bi-exponential model; and the distributed diffusion coefficient (DDC) and water molecular diffusion heterogeneity index (α) from a stretched exponential model. The parameters were compared between hepatic hemangiomas and liver metastases., Results: In total, 64 focal hepatic lesions were evaluated, of which 22 were identified to be hepatic hemangiomas and 42 were liver metastases. ADC, D, f, and DDC values were significantly lower in liver metastases than in hepatic hemangiomas (P <  0.0001, <  0.0001, 0.015, and <  0.0001, respectively); whereas, the α value was significantly higher in liver metastases than in hepatic hemangiomas (P =  0.028). The areas under the ROC curve (AUCs) for differentiating hepatic hemangiomas and liver metastases in ADC, D, D*, f, DDC, and α were 0.940, 0.908, 0.608, 0.686, 0.952, and 0.667, respectively. The AUC values of ADC and DDC were significantly greater than those of D* (P <  0.0001), f (P =  0.0001), and α values (P =  0.0001)., Conclusion: ADC and DDC values from the mono-exponential and stretched exponential models could be considered as quantitative imaging biomarkers for differentiating hepatic hemangiomas and liver metastases., (Copyright © 2021. Published by Elsevier B.V.)

Insulin receptor (IR) pre-mRNA undergoes alternative splicing that produces two isoforms, IR-A and IR-B. The ratio of IR-A to IR-B varies among tissues, which strongly suggests that IR mRNA alternative splicing is regulated in a tissue-specific manner. However, the precise molecular mechanism for IR alternative splicing remains to be elucidated, especially in liver. In this study, we have analyzed IR alternative splicing mechanism by preparing a mini-gene splicing reporter with rat genomic DNA. The splicing reporter that contains exon 11 and its flanking intronic sequences could reproduce alternative splicing pattern in rat hepatoma H4IIE cells. Introducing several deletions in introns of the reporter revealed that intron 11 contains the region near exon 11 essential to promote exon 11 inclusion. This region contains an UGCAUG sequence, a specific binding site for the Rbfox splicing regulator, and mutation in this sequence results in exon 11 skipping. Furthermore, RbFox2 knockdown in H4IIE cells enhanced exon 11 skipping of endogenous IR pre-mRNA. Lastly mutations in the SRSF3 binding site of exon11 together with the Rbfox2 binding site completely abolished exon 11 inclusion with a mini-gene reporter pre-mRNA. Our results indicate that RbFox2 and SRSF3 proteins mediate exon 11 inclusion in rat hepatoma cells., Competing Interests: Declaration of competing interest All authors have no conflicts of financial interest., (Copyright © 2021 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Objectives: To determine the optimal scan delay corresponding to individual hemodynamic status for pancreatic parenchymal phase in dynamic contrast-enhanced CT of the abdomen., Methods: One hundred and fourteen patients were included in this retrospective study (69 males and 45 females; mean age, 67.9 ± 12.1 years; range, 39-87 years). These patients underwent abdominal dynamic contrast-enhanced CT between November 2019 and May 2020. We calculated and recorded the time from contrast material injection to the bolus-tracking trigger of 100 Hounsfield unit (HU) at the abdominal aorta (s) (Time TRIG ) and scan delay from the bolus-tracking trigger to the initiation of pancreatic parenchymal phase scanning (s) (Time SD ). The scan delay ratio (SDR) was defined by dividing the Time SD by Time TRIG . Non-linear regression analysis was conducted to assess the association between CT number of the pancreas and SDR and to reveal the optimal SDR, which was ≥120 HU in pancreatic parenchyma., Results: The non-linear regression analysis showed a significant association between CT number of the pancreas and the SDR ( p < 0.001). The mean Time TRIG and Time SD were 16.1 s and 16.8 s, respectively. The SDR to peak enhancement of the pancreas (123.5 HU) was 1.00. An SDR between 0.89 and 1.18 shows an appropriate enhancement of the pancreas (≥120 HU)., Conclusion: The CT number of the pancreas peaked at an SDR of 1.00, which means Time SD should be approximately the same as Time TRIG to obtain appropriate pancreatic parenchymal phase images in dynamic contrast-enhanced CT with bolus-tracking method., Advances in Knowledge: The hemodynamic state is different in each patient; therefore, scan delay from the bolus-tracking trigger should also vary based on the time from contrast material injection to the bolus-tracking trigger. This is necessary to obtain appropriate late hepatic arterial or pancreatic parenchymal phase images in dynamic contrast-enhanced CT of the abdomen.

Purpose: To compare the detectability of pancreatic ductal adenocarcinoma (PDAC) and liver metastases between Gd-EOB-DTPA- and extracellular contrast materials (ECCMs) contrast-enhanced MR imaging contrast., Methods: Two hundred seventy-two patients with suspected pancreatic disease underwent Gd-EOB-DTPA-enhanced MR imaging (EOB group, n = 79) or ECCMs-enhanced MR imaging (ECCM group, n = 193). The ECCM group were administered the following contrast agents: Gd-DTPA (n = 158), Gd-BT-DO3A (n = 28), Gd-DOTA (n = 5), and Gd-DTPA-BMA (n = 2). Signal intensities of pancreatic parenchyma, paraspinal muscle, PDAC (if present), and background noise were measured. The signal intensity ratio (SIR) of the pancreas and tumor-to-pancreas contrast-to-noise ratio (CNR) were also calculated. If present, the conspicuity of PDAC was evaluated with the arterial dominant phase images. Liver metastases, if present, were also evaluated for all sequences. Qualitative and quantitative imaging parameters were compared between EOB and ECCM groups., Results: SIR of the pancreas (P < 0.001) and CNR (P = 0.0037) were significantly lower in EOB group when compared with the ECCM group. However, the sensitivity (97.1% vs. 93.5%, P = 0.42) and specificity (100.0% vs. 99.2%, P = 1.00) for detecting PDAC were not significant between EOB and ECCM groups. The EOB group showed a significantly greater sensitivity for detecting liver metastases compared with the ECCM group (95.0% vs 84.5%, P = 0.04) when evaluating on a lesion-by-lesion basis., Conclusion: Gd-EOB-DTPA-enhanced MR imaging performed similarly to ECCMs-enhanced MR imaging in detecting PDAC but had better sensitivity in detecting liver metastases.

A 72-year-old man was admitted to the hospital with fatigue. Colonoscopy revealed a 50 × 50 mm rectal tumor with bleeding. Based on close inspection, he was diagnosed with unresectable advanced rectal cancer with multiple liver metastases. Chemotherapy was administered as 10 cycles of bevacizumab + mFOLFOX6 and 7 cycles of bevacizumab + FOLFIRI. Nine months later, he presented with hematochezia and progression of anemia. It was difficult to stop the bleeding via endoscopy. He underwent radiation therapy (39 Gy in 13 fractions), and hemostasis was confirmed. Then, further chemotherapy was performed with 3 cycles of bevacizumab + FOLFIRI and 2 cycles of TAS102. However 14 months after the initial visit, he presented with right hypochondralgia and abdominal fullness due to the progression of multiple liver metastases. Palliative low-dose whole-liver radiation therapy (WLRT) (30 Gy in 10 fractions) was performed. He developed Grade 2 nausea, but his right hypochondralgia reduced, liver dysfunction improved, and he successfully completed radiotherapy. At approximately the same time his anemia progressed, and colonoscopy revealed recurrent bleeding from the tumor. Re-irradiation (15 Gy in 5 fractions) of the rectal tumor was carried out and a blood transfusion was performed for the bleeding. He was discharged after confirmation the anemia had not progressed. Few reports have been published on the use of both palliative re-irradiation to stop bleeding from rectal cancer and palliative low-dose WLRT. Based on our experience with this case, we believe that palliative radiotherapy can be useful in treating patients with a poor prognosis.

Purpose: To investigate iodine dose concentration required for adequate hepatic parenchymal enhancement on fast-kilovoltage-switching dual-energy computed tomography (DECT) of the abdomen based on patient body weight., Materials and Methods: The protocol of this prospective study was approved by the local Institutional Review Board and written informed consent for study participation was obtained from all patients. The study cohort of 204 consecutive patients who underwent whole body single-source DECT to screen for tumor metastases and/or recurrence after surgical resection of malignant tumors were randomly assigned to one of three protocols according to the iodine dose (400, 500, and 600 mgI/kg). For each case, two radiologists quantitatively and qualitatively reviewed three energy levels (65, 70, and 75 kilo electron volt [keV]) of the portal venous phase virtual monochromatic images (VMIs). CT numbers of the liver and the qualitative hepatic parenchymal enhancement were compared among the VMIs with the three protocols and three energy levels., Results: Hepatic enhancement (ΔHU > 50HU) was achieved at 65 keV with 400, 500, and 600 mgI/kg, at 70 keV with 500 and 600 mgI/kg, and at 75 keV with 600 mgI/kg. The hepatic parenchymal enhancement was graded as sufficient hepatic enhancement in 97%, 100%, and 99% at 65 keV with 400, 500, and 600 mgI/kg, 88% and 97% at 70 keV with 500 and 600 mgI/kg, and 84% at 75 keV with 600 mgI/kg, respectively., Conclusion: The iodine dose can be reduced to 400 mgI/kg at 65 keV or 500 mgI/kg at 70 keV in DECT without compromising hepatic parenchymal enhancement., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the value of view-sharing multi-hepatic arterial-phase (mHAP) imaging for diagnosis of hypervascular hepatocellular carcinoma (HCC)., Materials and Methods: Forty-seven consecutive patients with HCC underwent gadoxetic acid-enhanced magnetic resonance (MR) imaging before angiographic and lipiodol CT. Hepatic arterial-phase images were obtained at 5 consecutive phases with shared central k-space of 25%, followed by portal venous, late (2 and 3min), and hepatobiliary phase imaging. One-hundred-eight HCC nodules (size: 5-88mm, mean size: 18.2mm) confirmed on angiographic CT and lipiodol CT were evaluated for LI-RADS category and compared with single arterial-phase and mHAP findings regarding wash out, capsule, corona enhancement, and image quality., Results: Twenty-four HCCs (22.2%) (size: 6-19mm, mean size: 12.3mm) were categorized as LR-3 based on the single arterial-phase. Capsule appearance (25.9%) and washout (57.4%) were most frequently observed in late phase (2min). Corona enhancement was observed in 73.1% of all HCCs on mHAP. For the 24 HCCs of LR-3, corona enhancement was observed in 75% on mHAP and contributed to upgrade category. No significant difference was found in the frequency of corona enhancement between mHAP and angiographic CT (P=0.11). Image quality was valued as good or excellent in all cases., Conclusion: View-sharing mHAP was feasible without compromising image quality and contributed to the improvement in diagnostic confidence for hypervascular HCC in gadoxetic acid-enhance MR imaging., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The outcome after surgical resection for intrahepatic cholangiocarcinoma has not been satisfactorily evaluated due to its malignant behavior. Surgical resection, however, has the potential to improve the prognosis and may allow surgeons to experience rare cases with long survival. This report presents the case of a patient who developed recurrence 9 years after resection of intrahepatic cholangiocarcinoma. A 76-year-old female was diagnosed to have intrahepatic cholangiocarcinoma and underwent an extended right posterior subsegmentectomy. The gross appearance showed a mass-forming type tumor. The histopathological examination revealed well to moderately differentiated adenocarcinoma associated with portal vein invasion. Subcutaneous metastasis in the head as the first sign of relapse was diagnosed 9 years after hepatectomy. The histopathological findings of the subcutaneous tumor were similar to those of the intrahepatic cholangiocarcinoma, thus suggesting metastasis from intrahepatic cholangiocarcinoma. Positron emission tomography with 2-[fluorine-18]-fluoro-2-deoxy-D-glucose was useful for detecting multiple metastases. Long-term follow-up for more than 5 years is recommended because the present case shows that late recurrence of intrahepatic cholangiocarcinoma occurs even 5 years after resection.

The human glycine-N-acyltransferase (hGLYAT) gene and two related-genes (GLYATL1 and GLYATL2) were isolated. Human GLYAT, GLYATL1, and GLYATL2 cDNAs were isolated and shown to encode polypeptides of 295, 302, and 294 amino acids, respectively. GLYAT catalyzes glycine-N-acyltransfer reaction with benzoyl-CoA acting as a typical aralkyl transferase, while GLYATL1 catalyzed glutamine-N-acyltransfer reaction with phenylacetyl-CoA as an arylacetyl transferase. GLYAT was shown to be expressed specifically in the liver and kidney, and the cellular localization of GLYAT protein was restricted to the mitochondria. Interestingly, labeling using highly affinity purified anti-GLYAT antibody revealed that GLYAT expression was suppressed in all hepatocellular carcinomas, but not in other liver diseases. hGLYAT repression in cancerous cells in the liver was controlled at the transcriptional level. hGLYAT is a good candidate as a novel marker of hepatocellular carcinoma and may be a key molecule in the transition between differentiation and carcinogenesis of liver cells., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Extended left hepatectomy including the middle hepatic vein (MHV) may potentially induce right paramedian sector congestion of the remnant liver., Methods: To prevent venous congestion in the right paramedian sector, we performed extended left hepatectomy including the left hemiliver and anterior segment, which drain into the MHV and left hepatic vein (LHV), for 15 patients., Results: In 11 of 15 patients (73%), temporary clamping of the common trunk of the MHV and LHV and the proper hepatic artery provided the anterior fissure. Regeneration rate of the middle segment was similar to that of the right lateral sector (10.8% vs 11.2%) on postoperative computed tomography (CT) after 3 months., Conclusions: This procedure could represent a useful method for preventing postoperative venous congestion., (Crown Copyright (c) 2010. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine whether early primary pancreatic tumor resection can prevent liver metastases of intrapancreatic transplantation in a hamster model., Methods: Cells from the PGHAM-1 cell line were transplanted into the pancreases of 30 Syrian golden hamsters. A suspension of 5 x 10(6) cells was injected into the splenic lobe of each pancreas. The primary pancreatic tumor was resected in 15 of the hamsters 10 days after transplantation (resection group). Fifteen other animals with transplantation but without resection served as controls (control group). All hamsters were killed 21 days after transplantation. The primary pancreatic tumors were measured for size and volume and examined histologically and immunohistologically for angiogenesis and tumor proliferation., Results: In the resection group, small pancreatic tumors 4.7 +/- 0.94 mm in diameter were found and resected 10 days after transplantation. Neither pancreatic tumors nor liver metastases were found in the resection group at the end of the experiment. All animals in the control group had pancreatic tumors 12.3 +/- 3.29 mm in size, and 11 of 15 (73.3%) had liver metastases. The primary pancreatic tumors in the group with liver metastasis were significantly larger in diameter and volume than those in this group without liver metastasis (p<0.01). In the control group, proliferation of the primary pancreatic tumor, evaluated according to argyrophilic nucleolar organizer region, showed no differences within the pancreatic tumor group. On the other hand, the microvessel density of pancreatic tumors with liver metastases was significantly higher than that of tumors without liver metastases., Conclusions: Our results suggest that 10 days after transplantation, the pancreatic tumors were small in size and volume and ready to proliferate but not yet ready to begin metastasizing through angiogenesis. This is one reason why early resection of the primary tumor prevents liver metastasis.

Sarcomatous hepatocellular carcinoma is a rare neoplasm of the liver. A 79-year-old man with a liver tumor was admitted to our hospital. Enhanced computed tomography and magnetic resonance imaging revealed a cystlike lesion, whereas abdominal ultrasonography revealed a solid tumor. The patient underwent medial segmentectomy of the liver for the presumptive diagnosis of atypical hepatocellular carcinoma. Microscopically, the tumor was diagnosed as hepatocellular carcinoma with sarcomatous change. Although anticancer therapy is presumed to be a cause of sarcomatous change in hepatocellular carcinoma, some cases in which patients had not previously undergone anticancer therapy have been reported. Here we report a case of sarcomatous hepatocellular carcinoma without previous anticancer therapy and present a review of the literature.

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.

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.

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.)

Purpose: To correlate the perilesional hyperintense rim of malignant hepatic tumors seen on ferumoxide-enhanced T1-weighted gradient-echo (GE) MR images with histopathologic findings., Materials and Methods: In 13 tumors in 12 patients, T1-weighted GE images (TE of 1.4 msec, flip angle of 90 degrees) obtained after IV administration of ferumoxide were evaluated. MR imaging was initiated within one hour of the completion of ferumoxide administration. Surgical resection for tumors was performed within an interval of two weeks of the MR imaging. Resected specimens were histopathologically examined for peritumoral sinusoidal congestion, desmoplastic reaction, compressed hepatic parenchyma, lymphocytic infiltration, and vascular proliferation., Results: In twelve tumors (92%), prominently (N = 2), moderately (N = 5), and mildly to minimally (N = 5), a perilesional hyperintense rim was observed. Among histopathologic findings, the degree of peritumoral sinusoidal congestion correlated (R =.75, P <.04) with the degree of perilesional hyperintense rim. The thickness of the perilesional hyperintense rim showed a moderate positive correlation (R =.65, P <.02) with the thickness of peritumoral area with sinusoidal congestion., Conclusion: Perilesional hyperintense rim of malignant hepatic tumors on ferumoxide-enhanced T1-weighted GE images may correlate with sinusoidal congestion surrounding malignant hepatic tumors., (Copyright 2003 Wiley-Liss, Inc.)

The present study was performed to investigate the relationship between diabetes mellitus (DM) and primary hepatocellular carcinoma (HCC). Incident HCC cases were recruited in Kyushu, Japan. Ethnicity-, age-, gender-, residence-matched hospital controls and community controls were collected. Information on viral hepatitis B (HBsAg) or viral hepatitis C infection, history of blood transfusion, past histories including DM, amount of drinking or smoking, and genotypes of alcohol metabolizing enzymes was collected. Associations between these items and HCC were analyzed multivariately by conditional logistic regression analysis. Two hundred and twenty two (177 males and 45 females) case-control sets were completed between July 1995 and June 2000. Since hospital controls turned out to be a biased one or those sampled from a DM-prone population, a multivariate analysis was performed for the HCC-community controls sets, and it yielded significantly elevated odds ratio (OR)s due to past histories of DM (2.522; 95% Confidence Interval (CI) = 1.267-5.020), blood transfusion (1.747; 1.136-2.689), and unit increment of alcohol consumption (1.358; 1.096-1.684) for males. The same analyses of the HCC-community-controls sets for females, revealed an elevated but not statistically significant OR due to past histories of DM (4.195; 0.808-21.805). A multivariate analysis revealed that DM might be a risk factor for HCC.

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.)

We report and assess the imaging findings in a patient with multiple arterioportal shunting mimicking multiple hypervascular tumors that showed multiple areas of hyperintensity with gadolinium-enhanced gradient-recalled-echo images obtained in the hepatic arterial phase and corresponding areas of slight hyperintensity with T2-weighted images.

A comparison of responses obtained in interviews using a structured questionnaire and those obtained using a self-administered questionnaire about parental history of liver diseases and personal smoking and drinking habits was made to evaluate whether the self-administered questionnaire is an effective means for collecting information on these variables in place of an interview. The subjects used in the present analyses were 46 male hepatocellular carcinoma (HCC) cases and 46 hospital controls who were interviewed between January, 1996 and January, 1997 for HCC cases and between January, 1996 and April, 1997 for hospital controls. Ages at start or stop of smoking and drinking were grouped into four categories as categorical variables. The cumulative number of cigarettes and cumulative alcohol consumption were also grouped into four categories. Generally speaking, the degree of agreement was substantially high for both categorical and continuous variables, particularly for parental history of liver diseases, and smoking (ICC = 0.929 and 0.912 for cases and controls, respectively) and drinking (ICC = 0.899 and 0.882, respectively) habits that are originally nominal categorical variables. On the other hand, the cumulative number of cigarettes (ICC = 0.928 and 0.716, respectively) and the cumulative alcohol consumption (ICC = 0.761 and 0.825, respectively) seemed to have a lower degree of agreement than other variables. For these variables, there was a tendency for the self-administered questionnaire to produce larger values compared with the interview. Therefore, the self-administered questionnaire seemed to be an effective means for collecting information on categorical variables, while the interview using a structured questionnaire seemed to be preferable to the self-administered questionnaire with regard to the lifetime exposure to cigarettes and alcohol.

MR imaging, which is able to evaluate T1- and T2-relaxation time, fat, hemorrhage, metal deposition, blood flow, perfusion, diffusion, and so on, has offered more information for the diagnosis of diffuse and focal hepatic diseases than CT. The spoiled-GRE sequence with high contrast resolution and ease of the aimed contrast capture derived from the k-space property, with the use of a phased-array multicoil, have remarkably increased the value of gadolinium-enhanced dynamic MR diagnosis of the liver. In recent years, the clinical use of ferumoxide has begun, and issues concerning the superiority or inferiority and combination of contrast media are being debated. This paper describes the value, role, and clinical practice of unenhanced, gadolinium-enhanced, and ferumoxide-enhanced MR imaging of the liver based on knowledge obtained in our institution, with some reference to the literature.

Objective: The purpose of our study was to compare how well gadolinium-enhanced and ferumoxide-enhanced MR imaging reveal malignant hepatic tumors., Subjects and Methods: Both gadolinium-enhanced and ferumoxide-enhanced MR imaging were separately performed in 53 patients with a total of 87 malignant hepatic tumors (57 hepatocellular carcinomas, 28 metastases, two cholangiocarcinomas). Thirty-one of the 53 patients had hepatic cirrhosis. Images were reviewed by three independent off-site observers. Observer performance was evaluated by means of sensitivity, specificity, and receiver operating characteristic curve analyses., Results: Gadolinium-enhanced MR imaging outperformed ferumoxide-enhanced MR imaging in sensitivity (81% versus 62%, p < 0.01) for malignant-tumor detection. Specificity was comparable (94%) between the two types of MR imaging. Area under receiver operating characteristic curve (A(z)) value was significantly higher with gadolinium-enhanced MR imaging than with ferumoxide-enhanced MR imaging in patients overall (A(z) = 0.896 versus 0.805, p < 0.001), in patients with cirrhosis (A(z) = 0.907 versus 0.807, p < 0.001), and in patients without cirrhosis (A(z) = 0.899 versus 0.834, p < 0.01). The superiority was enhanced in the subset of patients with cirrhosis., Conclusion: Gadolinium-enhanced MR imaging outperforms ferumoxide-enhanced MR imaging in revealing malignant hepatic tumors. Gadolinium-enhanced MR imaging is recommended, particularly for patients with cirrhosis.

Aims: The purpose of our study was to evaluate the observer performance with combined helical CT during arterial portography (CTAP) and biphasic CT hepatic arteriography (CTHA) in the pre-operative detection of malignant hepatic tumours., Methods: Computed tomography images obtained in 41 patients with suspected hepatic tumours were retrospectively reviewed. In a blind fashion, three off-site, independent radiologists reviewed CTAP and early-phase CTHA combined for the first review, then late-phase CTHA was added for the second review. Statistical analysis was conducted on lesion-by-lesion and segment-by-segment bases; a total of 328 liver segments including 65 segments with 74 malignant hepatic tumours ranging in size from 5 to 100 mm (mean, 21.4 mm) were analysed., Results: Sensitivity for detection of liver segments harbouring tumours of CTAP and biphasic CTHA combined (82%) was identical to that of CTAP and early-phase CTHA combined (82%). Specificity of CTAP and biphasic CTHA combined (93%) was greater than that of CTAP and early-phase CTHA combined (90%, P < 0.005). The mean confidence level for the 74 tumours significantly increased by adding late-phase CTHA (P < 0.0005). The mean confidence level for 100-142 benign perfusion abnormalities detected with CTAP and early-phase CTHA combined significantly decreased by adding late-phase CTHA (P < 0.0005)., Conclusion: By combining late-phase CTHA with CTAP and early-phase CTHA information, the specificity for the detection of malignant hepatic tumours rises significantly, allowing more accurate preoperative tumour detection., (Copyright 2001 The Royal College of Radiologists.)

The purpose of our study was to compare observer performance in the detection of malignant hepatic tumors with ferumoxides-enhanced magnetic resonance (MR) images obtained with proton density-weighted spin-echo (SE), T2-weighted fast SE, T2*-weighted gradient-recalled-echo (GRE), and proton density-weighted echo-planar (EP) sequences. Ferumoxides-enhanced MR images obtained with the four sequences in 50 patients with 92 solid malignant and 64 nonsolid benign lesions were retrospectively analyzed. Image review was conducted on a segment-by-segment basis; a total of 397 liver segments was reviewed separately for solid and nonsolid lesions by three independent readers. Observer performance was evaluated with receiver operating characteristic analysis. Lesion-to-liver contrast-to-noise ratio was higher with SE and EP than with GRE and fast SE images for solid lesions (P < 0.05), and higher with fast SE and SE than with GRE images for nonsolid lesions (P < 0.01). Proton density-weighted SE and T2-weighted fast-SE images were superior to T2*-weighted GRE and proton density-weighted EP images for detection of malignant hepatic tumors. T2-weighted fast SE images were the best for detection of nonsolid lesions. T2-weighted fast SE images that were comparable to proton density-weighted SE images for solid tumor detection, that were the best for nonsolid lesion detection, and that had an acquisition time of one third to half of that of SE imaging may be able to replace SE images for ferumoxides-enhanced liver imaging.

We retrospectively investigated the appearance and frequency of atypically enhancing cavernous hemangiomas with high-spatial-resolution (512x224 matrix) gadolinium-enhanced triphasic dynamic gradient-recalled-echo (GRE) MR images. Images of 132 hepatic cavernous hemangiomas (ranging in size from 4 to 72 mm; mean size 17.2 mm) in 95 patients (42 men and 53 women; age range 25-85 years; mean age 54 years) were retrospectively reviewed by two independent radiologists. Forty (30%) of 132 lesions atypically enhanced. Smaller hemangiomas (< or =15 mm) more frequently (29%) showed early entire enhancement with or without arterio-portal shunting in the hepatic arterial-dominant phase ( p<0.001); most of them showed hyperintense complete fill-in in the equilibrium phase and were readily characterized. "Bright dot" or minimal peripheral enhancement in the equilibrium phase was seen in a small number of lesions (6% each). With T2-weighted images, 130 (98%) lesions showed moderately to very high signal intensity and only 2 (2%) with minimal peripheral enhancement showed hyperintensity of slight degree. The high-spatial-resolution dynamic GRE images clearly revealed minute enhancement characteristics of hemangiomas. Although moderately to very high signal intensity with T2-weighted MR images is informative for the diagnosis of most cavernous hemangiomas, when a lesion shows minimal peripheral enhancement in the equilibrium phase and hyperintensity of slight degree with T2-weighted images, further follow-up or biopsy may be warranted to discriminate hypovascular metastases.

The purpose of our study was to evaluate the supplementary value of breath-hold fat-suppressed T2-weighted magnetic resonance (MR) imaging with half-Fourier single-shot fast spin-echo (SE) or multishot SE echoplanar (EP) sequences combined with respiratory-triggered fat-suppressed fast SE T2-weighted MR imaging for detection and characterization of focal hepatic lesions. MR images in 42 patients with 82 solid, malignant and 77 nonsolid, benign lesions were analyzed. Image review was conducted on a segment-by-segment basis; in all, 333 liver segments were reviewed separately for solid and nonsolid lesions by three independent radiologists. For solid lesions, observer performance with receiver-operating-characteristic (ROC) analysis in one radiologist and specificity in another significantly improved after adding single-shot fast SE images. For nonsolid lesions, observer performance with ROC analysis in one radiologist and specificity in another significantly improved after adding single-shot fast SE images. Combining breath-hold half-Fourier single-shot fast SE imaging with respiratory-triggered fast SE imaging may be recommended for improved detection and characterization of focal hepatic lesions. J. Magn. Reson. Imaging 2000;12:444-452., (Copyright 2000 Wiley-Liss, Inc.)

Objective: We compared radiologists' performance on combined unenhanced, gadolinium-enhanced, and ferumoxides-enhanced MR imaging with their performance on helical CT during arterial portography (CTAP) and biphasic CT during hepatic arteriography (CTHA) for the preoperative detection of malignant hepatic tumors., Subjects and Methods: MR images and CT scans obtained in 33 patients were retrospectively analyzed. Images of the liver were reviewed on a segment-by-segment basis; a total of 261 segments with 39 hepatocellular carcinomas and 21 metastases were independently reviewed by three radiologists who were invited from outside institutions. Unenhanced and gadolinium-enhanced MR images were reviewed first, then ferumoxides-enhanced MR images were added for combined review. CTAP images and biphasic CTHA images were reviewed together., Results: Sensitivity for the detection of hepatic tumors was analogous for combined unenhanced, gadolinium-enhanced, and ferumoxides-enhanced MR images (86%) and for combined CTAP images and biphasic CTHA images (87%). Specificity was higher with MR images (95%, p < 0.01) than with CT images (91%). Radiologists' performances were improved (Az = 0.962, p = 0.0502) by combining ferumoxides-enhanced MR images with unenhanced and gadolinium-enhanced MR images (Az = 0.950), and were analogous for combined unenhanced, gadolinium-enhanced, and ferumoxides-enhanced MR images and for combined CTAP images and biphasic CTHA images (Az = 0.959)., Conclusion: Radiologists' performances on combined unenhanced, gadolinium-enhanced, and ferumoxides-enhanced MR imaging compared with their performances on combined helical CTAP and biphasic CTHA are analogous for the preoperative detection of malignant hepatic tumors. Such a dedicated combination of MR imaging may obviate the need for more invasive angiographically assisted helical CT for the preoperative detection of malignant hepatic tumors.

This paper deals with a study to obtain the optimal sequence of gradient echo (GE) for T1- and T2*-weighted images similar to T1- and T2-weighted images of spin echo (SE). Two GE sequences, fast low angle shot (FLASH) and fast imaging with steady-state precession (FISP), were performed in 15 cases of liver metastasis in various combination of flip angle (FA), repetition time (TR), and echo time (TE). The optimal combinations were summarized as follows: 1) T1-weighted FLASH image with FA of 40 degrees, TR of 22 msec and TE of 10 msec, 2) T1-weighted FISP image with FA of 70 degrees, TR of 100 msec, TE of 10 msec, 3) both T2*-weighted FLASH and FISP images with FA of 10 degrees, TR of 100 msec and TE of 30 msec. Not only to provide the adequate T1- and T2*-weighted images but also to enable breath-holding MR imaging, GE sequences can optionally take place SE in cases of deteriorated images caused by moving artifacts. Other applications support the re-examination and further detailing when required, conveniently rather in short time.