Hypervascular Hypervascular Hepatocellular Carcinoma Research Articles

Low contrast dose protocol involving a 100kVp tube voltage for hypervascular hepatocellular carcinoma in patients with renal dysfunction.

To evaluate the feasibility of a 20% reduced contrast dose hepatic arterial phase (HAP) CT for hypervascular hepatocellular carcinoma (HCC) with 100 kVp. The study included 97 patients with hypervascular HCC who underwent dynamic CT, including HAP scanning. The 54 patients had an estimated glomerular filtration rate (eGFR) of ≥60 were scanned with our conventional 120 kVp protocol. The other 43 patients (eGFR<60) underwent scans using a tube voltage of 100 kVp and a 20% reduced contrast dose. We compared the estimated effective dose, image noise, tumor-liver contrast (TLC), and contrast-to-noise ratio (CNR) in the hepatic arterial phase between the two groups using the Student's t test. Estimated effective dose and image noise were not significantly different between these groups (p = 0.67 and p = 0.20, respectively). The TLC and CNR were significantly higher for the 100 kVp protocol than for the 120 kVp protocol (52.2 HU ± 17.4 vs 40.8 HU ± 18.6, p < 0.01 and 6.8 ± 2.6 vs 5.5 ± 2.4, p = 0.01, respectively). For hepatic arterial phase CT of hypervascular HCC, 100 kVp scan allows a 20% reduction in the contrast dose without reduction in image quality compared with a standard 120 kVp CT protocol.

Diffusion kurtosis imaging to assess response to treatment in hypervascular hepatocellular carcinoma.

The objective of our study was to compare diffusion kurtosis imaging (DKI) with conventional diffusion-weighted imaging (DWI) for assessing the response to treatment in hypervascular hepatocellular carcinoma (HCC). Sixty-two consecutive patients with treated or untreated hypervascular HCC underwent MRI of the liver including DKI (b values of 0, 100, 500, 1000, 1500, and 2000 s/mm(2)). The mean kurtosis (MK) and apparent diffusion coefficient (ADC) values of the hepatic parenchyma and of the HCCs were computed. The detectability of viable HCC based on MK and ADC values was compared. We also assessed the correlation between Child-Pugh grades and MK or ADC values. For a total of 112 HCC nodules (viable, n = 63; nonviable, n = 49), the MK value was significantly higher for the viable group (mean ± SD, 0.81 ± 0.11) than for the non-viable group (0.57 ± 0.11) (p < 0.001). The mean ADC value was significantly lower for the viable group (1.44 ± 0.42 × 10(-3) mm(2)/s) than for the nonviable group (1.94 ± 0.52 × 10(-3) mm(2)/s) (p < 0.001). The sensitivity, specificity, and AUC of the ROC curve for the assessment of HCC viability were greater (p < 0.001) using MK (85.7%, 98.0%, and 0.95, respectively; cutoff value = 0.710) than using ADC (79.6%, 68.3%, and 0.77, respectively; cutoff value = 1.535 × 10(-3) mm(2)/s). Although the ADC of hepatic parenchyma was lower in patients with Child-Pugh grade B or C disease than in those with grade A disease (p = 0.02), no significant difference in MK (p = 0.45) was found among the Child-Pugh grades. DKI can be a new option for the assessment of posttherapeutic response in HCC.

Imaging features of subcentimeter hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase MR imaging that progress to hypervascular hepatocellular carcinoma in patients with chronic liver disease.

With the advent of 3-T magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI), many subcentimeter hepatic nodules have been frequently detected in patients with chronic liver disease, and the prediction of subcentimeter nodules that progress to hypervascular hepatocellular carcinoma (HCC) is important. To reveal the imaging features of subcentimeter hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase MR images in patients with chronic liver disease that may be related with progression to hypervascular HCC. This study included 109 patients with 135 subcentimeter hypointense nodules (103 hepatocellular carcinomas [HCCs] and 32 benign nodules) on gadoxetic acid-enhanced hepatobiliary phase. For each subcentimeter nodule, the following imaging features were analyzed: (i) hyperintensity on T2-weighted (T2W) image or DWI; (ii) arterial hypervascularization; and (iii) hypointensity on a portal or late phase. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of those imaging features for predicting subcentimeter nodules that progressed to hypervascular HCC were evaluated. Volume doubling time (VDT) of subcentimeter nodules that progressed to hypervascular HCC was compared to that of growing benign nodules. Arterial hypervascularization with washout yielded the highest specificity (90.6%) and PPV (95.4%) for prediction of subcentimeter nodules that progressed to hypervascular HCC. Combining hyperintensity on T2W image or DWI and arterial hypervascularization with washout did not raise the specificity (90.6%) for prediction of subcentimeter nodules that progressed to hypervascular HCC. Mean VDT (112.2 ± 106.3 days) of subcentimeter nodules that progressed to hypervascular HCC during follow-up was significantly shorter than those of benign subcentimeter nodules (1258 ± 766.5 days, P < 0.001). Arterial hypervascularization with washout in subcentimeter hypointense nodules on gadoxetic acid-enhanced hepatobiliary phase in patients with chronic liver disease is strongly related with progression to hypervascular HCC.

Was Hypervascular Hepatocellular Carcinoma Visible on Previous Gadoxetic Acid-Enhanced Magnetic Resonance Images?

Background: During the follow-up of patients with chronic liver disease, hypervascular hepatocellular carcinomas (HCCs) can develop either from pre-existing high-risk nodules or by de novo hepatocarcinogenesis. The purpose of this study was to evaluate, by retrospective analysis, the detectability and signal intensity on previous hepatocyte-phase gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) of hypervascular HCC initially detected on current EOB-MRIs. Methods: We examined 50 initially detected hypervascular HCCs that showed typical enhancement features on EOB-MRI in 39 patients whose previous EOB-MRI images obtained 6-19 months earlier were available. The detectability of each hypervascular HCC on the hepatocyte phase images of previous EOB-MRIs was assessed. The imaging features on hepatocyte-phase images of previous EOB-MRIs at the locations where hypervascular HCCs were found on the current EOB-MRI images were classified as detectable or undetectable. The signal intensities of detectable nodules (defined as group A) on hepatocyte-phase images of previous EOB-MRIs were classified as hypo-, iso-, or hyperintensity. Nodules undetectable on the hepatocyte-phase images of previous EOB-MRIs were assigned to group B. Results: Twenty-two (22/50, 44%) hypervascular HCCs were detectable on the earlier hepatocyte phase images (group A). In contrast, 28 (28/50, 56%) hypervascular HCCs were not detectable on the hepatocyte phase of earlier EOB-MRI images (group B). Conclusion: When the previous EOB-MRI images were used as the reference, more than half (28/50, 56%) of hypervascular HCCs initially appearing on the current EOB-MRI images were found not to have developed from nodules detectable on the previous MRIs through the traditionally accepted process of multistep carcinogenesis. Instead, they seemed to have developed via an “imaging-occult” process of carcinogenesis in patients with chronic liver diseases.

Clinical value of gadoxetic acid-enhanced magnetic resonance imaging in surgery for hepatocellular carcinoma - with a special emphasis on early hepatocellular carcinoma.

Gadoxetic acid- or gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (EOB-MRI) achieves excellent lesion detection and characterization for both hypervascular hepatocellular carcinoma (HCC) in arterial phase imaging and hypovascular early HCC (small well-differentiated HCC of the vaguely nodular type) in hepatobiliary phase imaging, and has become an indispensable imaging modality in the treatment of HCC. Early HCCs have been detected more frequently since the introduction of EOB-MRI into daily clinical practice. Early HCC is known to progress to conventional hypervascular HCC, and many risk factors have been identified for the hypervascularization of early HCC including the diameter of the tumor, presence of fat, and imaging findings of EOB-MRI. The rate of the development of hypervascular HCC was previously reported to be high in patients with chronic liver disease and early HCC. The presence of early HCC is regarded as a predictor for the recurrence of HCC following hepatic resection. On the other hand, although early HCC itself is currently not regarded as a target lesion for hepatic resection, early HCC at high risk of hypervascularity needs to be treated by local ablation therapy. If concomitant early HCC with progressed HCC is at high risk of hypervascularization and the functional liver reserve of a patient is sufficient, its simultaneous treatment at the time of hepatic resection for progressed HCC is recommended. Further studies on larger numbers of patients are needed before this strategy is adopted.

Incidence for progression of hypervascular HCC in hypovascular hepatic nodules showing hyperintensity on gadoxetic acid-enhanced hepatobiliary phase in patients with chronic liver diseases.

The purpose of this study was to elucidate the incidence and risk factors for the progression of hyperintense nodules, observed in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI), to hypervascular hepatocellular carcinoma (HCC). Hypovascular nodules (n = 157) showing hyperintensity in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were examined in 41 patients. All patients underwent computed tomography (CT) during hepatic arteriography and CT during arterial portography within one month of Gd-EOB-DTPA-enhanced MRI. The incidence of progression to hypervascular or classical HCC was calculated using the Kaplan-Meier method. Tumor size was determined by univariate and multivariate analysis to be an important risk factor of hypervascularization (p = 0.041, odds ratio 1.135). The cumulative incidences of hypervascularization in hypovascular nodules showing hyperintensity on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were 2.4, 4.5, and 6.2 % at 12, 24, and 36 months, respectively. The incidence of hypervascularization was significantly increased in nodules >10 mm in diameter (p = 0.00035). In patients with chronic liver disease, hypovascular nodules presenting as hyperintense in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI and >10 mm in diameter have malignant potential for progression to hypervascular HCC and require careful management.

Tumor Response on CT Following Hypofractionated Stereotactic Ablative Body Radiotherapy for Small Hypervascular Hepatocellular Carcinoma With Cirrhosis

The purpose of this study is to evaluate the CT appearances of tumor responses following hypofractionated stereotactic ablative body radiotherapy for small hypervascular hepatocellular carcinomas (HCCs) and to assess the relationship between tumor responses and local control. Among 277 HCC tumors treated with stereotactic ablative body radiotherapy (35 or 40 Gy per five fractions), we selected enhanced lesions on arterial phase CT performed before stereotactic ablative body radiotherapy. Radiographic findings after stereotactic ablative body radiotherapy were evaluated during a 2-year follow-up period with the modified Response Evaluation Criteria in Solid Tumors. Local control and survival rates were calculated with the Kaplan-Meier method. Forty-two tumors with a median size of 2.1 cm (range, 1.0-3.8 cm) were selected with a median follow-up of 23.3 months (range, 9-56 months). Local recurrence was observed in two tumors after achieving a complete response (CR). The 2-year local control rate was 97%, and the overall survival rate was 81%. CR increased from 10 (24%) to 28 (67%) to 30 (71%) tumors at 3, 6, and 12 months after stereotactic ablative body radiotherapy. Overall CR at maximum follow-up was 39 tumors (93%), yet three enhanced tumors persisted for more than 2 years. The median time to achieve CR was 5.9 months (range, 1.2-34.2 months). The CR rate in hypervascular HCCs after hypofractionated stereotactic ablative body radiotherapy increased during the 2-year follow-up period. Cautious and continuous observation until tumor regrowth is considered relevant to evaluate a true effect of this treatment. Further studies for the optimal evaluation of treatment outcome after stereotactic ablative body radiotherapy are warranted.

Optimal scan timing of hepatic arterial-phase imaging of hypervascular hepatocellular carcinoma determined by multiphasic fast CT imaging technique

A new multiphasic fast imaging technique, known as volume helical shuttle technique, is a breakthrough for liver imaging that offers new clinical opportunities in dynamic blood flow studies. This technique enables virtually real-time hemodynamics assessment by shuttling the patient cradle back and forth during serial scanning. To determine optimal scan timing of hepatic arterial-phase imaging for detecting hypervascular hepatocellular carcinoma (HCC) with maximum tumor-to-liver contrast by volume helical shuttle technique. One hundred and one hypervascular HCCs in 50 patients were prospectively studied by 64-channel multidetector-row computed tomography (MDCT) with multiphasic fast imaging technique. Contrast medium containing 600 mg iodine per kg body weight was intravenously injected for 30 s. Six seconds after the contrast arrival in the abdominal aorta detected with bolus tracking, serial 12-phase imaging of the whole liver was performed during 24-s breath-holding with multiphasic fast imaging technique during arterial phase. By placing regions of interest in the abdominal aorta, portal vein, liver parenchyma, and hypervascular HCCs on the multiphase images, time-density curves of anatomical regions and HCCs were composed. Timing of maximum tumor-to-liver contrast after the contrast arrival in the abdominal aorta was determined. For the detection of hypervascular HCC at arterial phase, mean time and value of maximum tumor-to-liver contrast after the contrast arrival were 21 s and 38.0 HU, respectively. Optimal delay time for the hepatic arterial-phase imaging maximizing the contrast enhancement of hypervascular HCCs was 21 s after arrival of contrast medium in the abdominal aorta.

Evaluation of Optimal Scan Delay for Gadoxetate Disodium–Enhanced Hepatic Arterial Phase MRI Using MR Fluoroscopic Triggering and Slow Injection Technique

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. 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. 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). 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.

Recommended Iodine Dose for Multiphasic Contrast-Enhanced Mutidetector-Row Computed Tomography Imaging of Liver for Assessing Hypervascular Hepatocellular Carcinoma: Multicenter Prospective Study in 77 General Hospitals in Japan

To determine the recommended iodine dose of contrast material (CM) for hepatic arterial-dominant phase (HAP) and hepatic parenchymal phase (HPP) imaging to assess hypervascular hepatocellular carcinoma (HCC). This was a prospective study including 348 patients with hypervascular HCC in 77 hospitals as a postmarketing surveillance to investigate the effects of body weight-tailored dose of CM (300 mgI/mL of iohexol) for hepatic multiphasic contrast-enhanced multidetector-row computed tomography imaging. Informed consent was obtained from all patients who were enrolled. The tumor-to-liver contrast (TLC) of HAP images was assessed qualitatively (QL-TLC) and quantitatively (QT-TLC [HU]; computed tomography [CT] value of tumor-CT value of hepatic parenchyma). Minimal and sufficient QT-TLC were defined as CT values corresponding to the median and 75% of QL-TLC assigned with "good," respectively. The recommended iodine dose was estimated by the relationship between iodine dose (mgI/kg) and QT-TLC. There was a good correlation between QL-TLC and QT-TLC. The recommended iodine dose of CM for HAP imaging was considered to be in the range of 567-647 mgI/kg based on minimal (33.7 HU) and sufficient QT-TLC (40.9 HU). Meanwhile, the recommended dose of CM for HPP imaging was 572 mgI/kg as a dose that gives hepatic enhancement more than 50 HU during HPP imaging. The recommended iodine dose of CM for HAP and HPP imaging may be different, being 567-647 mgI/kg and 572 mgI/kg, respectively, in assessing hypervascular HCC.

The efficacy of contrast protocol in hepatic dynamic computed tomography: multicenter prospective study in community hospitals

PurposeTo investigate four different contrast protocols to detect hypervascular hepatocellular carcinoma (HCC) most adaptable for patients at any body weight (BW) in clinical practice.Materials and methodsA post-marketing surveillance of liver dynamic CT was prospectively performed by four different protocols in 415 patients: Protocol-A, BW-tailored dose of contrast media (CM: iohexol 300 mgI/mL), fixed injection duration (30s), fixed scan timing at arterial phase (AP); Protocol-B, BW-tailored dose of CM, fixed injection duration (30s), by bolus tracking; Protocol-C, BW-tailored dose of CM, fixed injection flow rate, by bolus tracking; Protocol-D, 100 mL constant of CM at any BW, fixed scan timing. Scan timing and tumor conspicuity at AP was scored qualitatively. The quantitative CT values of aorta and tumor liver contrast (TLC) were obtained.ResultsThe qualitative rate assessed “good” as scan timing of AP in Protocol-C was significantly lower than those in Protocols A and D (difference:16.6%, 17.4%, P = 0.0069, P = 0.0140, respectively). Scatter plot of Protocol-D (R2 = 0.1283) at AP showed significant inverse relationship between TLC and BW (P =0.0053), although not significant in Protocols A, B, C.ConclusionIn patients with higher BW, protocols of BW-tailored dose of CM and/or fixed injection duration have no dependence on BW to diagnose hypervascular HCCs.Electronic supplementary materialThe online version of this article (doi:10.1186/2193-1801-2-367) contains supplementary material, which is available to authorized users.

Low Tube Voltage Intermediate Tube Current Liver MDCT: Sinogram-Affirmed Iterative Reconstruction Algorithm for Detection of Hypervascular Hepatocellular Carcinoma

The purpose of this study was to compare image quality and lesion detectability in the evaluation of hypervascular hepatocellular carcinoma (HCC) on low-tube-voltage half-dose liver CT scans subjected to sinogram-affirmed iterative reconstruction (SAFIRE) with the quality and detectability on full-dose scans reconstructed with filtered back projection (FBP). A total of 126 patients with suspected HCC who underwent liver CT including arterial phase scanning at 80 kVp in the dual-source mode (300 mAs for each tube) were included in the study. The half-dose arterial scans were reconstructed with FBP, iterative reconstruction in image space (IRIS), and five SAFIRE strengths (S1-S5) and were compared with full-dose virtual scans (600 mA) reconstructed with FBP. We assessed image noise, contrast-to-noise ratio (CNR) of the liver and blood vessels, and lesionto-liver CNR. Two radiologists evaluated image quality and lesion detectability attained with the different imaging sets. Image noise on SAFIRE images was significantly lower than that on the other images, and the CNRs on SAFIRE images were higher than those on half-dose FBP images (p < 0.001). In addition, lesion-to-liver CNR on the half-dose S5 SAFIRE images was higher than on IRIS and full-dose FBP images (p < 0.05). Among the half-dose scans, SAFIRE images had significantly better image quality than FBP images (p < 0.05). Regarding lesion detection, half-dose SAFIRE images were better than half-dose FBP images and were comparable with full-dose FBP images (observer 1, 91.8% vs 96%; observer 2, 98% vs 98%; p > 0.05). Performing half-dose 80-kVp liver CT with SAFIRE technique may increase image quality and afford comparable lesion detectability of hypervascular HCC at a reduced radiation dose compared with full-dose CT with FBP.

Volumetric low-tube-voltage CT imaging for evaluating hypervascular hepatocellular carcinoma; effects on radiation exposure, image quality, and diagnostic performance

To assess the value of hepatic arterial-phase (HAP) imaging with a low tube voltage (80 kVp), using non-helical, volumetric acquisition with a 320-detector-rows area-detector CT (ADCT) scanner for evaluating hypervascular hepatocellular carcinoma (HCC) compared with routine 120-kVp HAP imaging. This study enrolled 128 patients with 148 HCCs. Seventy-six patients with 79 HCCs underwent HAP imaging with 80 kVp obtained using a 320-detector-rows ADCT scanner. The remaining 52 patients with 69 HCCs underwent routine HAP imaging with 120 kVp obtained by 64-slice helical acquisition. Image noise and tumor to liver contrast-to-noise ratio (CNR) of the two sets of images were compared. Three radiologists evaluated both sets of images using receiver operating characteristic analyses. Although there was a two-fold increase in the mean image noise with 80 kVp over that with 120 kVp (p < 0.001), no significant differences were observed in CNR among the two sets. The mean area under the curve (Az value) and the sensitivity for detecting HCC with 80 kVp (0.980, 78/79, respectively) were higher than that of 120 kVp (0.892, 55/69, respectively). HAP imaging with 80 kVp obtained by an ADCT scanner significantly improves the diagnostic performance for evaluating hypervascular HCC.

Timing of the hepatic arterial phase at Gd‐EOB‐DTPA‐enhanced hepatic dynamic MRI: Comparison of the test‐injection and the fixed‐time delay method

To compare the fixed-time- and the test-injection method with respect to the image quality of hypervascular hepatocellular carcinoma (HCC) and the adequacy of timing of the hepatic arterial phase (HAP) in Gd-EOB-DTPA (EOB) enhanced MRI. We studied 63 patients with computed tomography (CT) -proven hypervascular HCC: 30 (group 1) were scanned HAP using the fixed-time delay method (protocol 1); in the other 33 (group 2), we applied the test-injection method (protocol 2). We compared the protocols with respect with tumor-to-liver contrast (TLC), contrast-to-noise-ratio (CNR), and relative enhancement of the liver and tumor (REL , RET ) during HAP. Two radiologists compared the adequacy of HAP, image contrast, image noise, and overall image quality. Under protocol 2, TLC, CNR, and REL and RET of hypervascular HCC were significantly higher (P < 0.01). The proportion of optimal HAP was significantly higher for protocol 2 than protocol 1 (P < 0.01). The visual score of the image contrast and the overall image quality were significantly higher in group 2 than group 1 (P = 0.02 and P = 0.01, respectively). At EOB-enhanced hepatic dynamic MRI, the test-injection method yielded better image quality of hypervascular HCC and improved adequacy of timing of HAP.

Newly Developed Hypervascular Hepatocellular Carcinoma During Follow-Up Periods in Patients With Chronic Liver Disease: Observation in Serial Gadoxetic Acid–Enhanced MRI

The purpose of our study was to evaluate the process and frequency of newly developed hypervascular hepatocellular carcinoma (HCC) in serial gadoxetic acid-enhanced MRI examinations in patients with chronic liver disease during clinical follow-up periods. After review of 341 MRI examinations in 100 patients with chronic liver diseases who underwent gadoxetic acid-enhanced MRI at least twice during the observation period, 32 newly developed hypervascular HCCs in 14 patients were retrospectively evaluated. Serial MRI examinations before detecting hypervascular HCC were evaluated to determine whether hypervascular HCC showed the presence of a hypointense nodule on the hepatobiliary phase and hypovascularity (high-risk nodule) before hyper-vascularization. The size of newly developed hypervascular HCCs and the duration of hyper-vascularization from initial detection of a high-risk nodule were compared between HCCs with and without the presence of a high-risk nodule. Eleven (34.4%) of 32 newly developed hypervascular HCCs had the presence of high-risk nodule before hypervascularization. The size of newly developed hypervascular HCCs was significantly smaller in HCC with high-risk nodule presence (mean, 9.5 mm) than in HCC without the presence of high-risk nodule (mean, 16.4 mm) (p = 0.004). In hypervascular HCCs with high-risk nodule presence, the mean duration of hypervascularization from initial high-risk nodule was 330.7 days, with mean size change from 5.4 mm of high-risk nodules to 9.5 mm of hypervascular HCCs. Approximately one third of newly developed hypervascular HCCs had the presence of high-risk nodule before hypervascularization in the serial gadoxetic acid-enhanced MRI examinations. High-risk nodule tended to develop into hypervascular HCC after having almost doubled in size during 1 year of high-risk nodule presence.

Presence of a hypovascular hepatic nodule showing hypointensity on hepatocyte‐phase image is a risk factor for hypervascular hepatocellular carcinoma

To determine whether the presence of a hypovascular nodule in the liver showing hypointensity on hepatocyte-phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) is a risk factor for hypervascular hepatocellular carcinoma (HCC) in patients with chronic liver disease. Forty-one patients with pathologically confirmed hypervascular HCC and 41 age- and gender-matched controls were retrospectively selected. These patients had undergone EOB-MRI at least twice: the latest EOB-MRI and EOB-MRI performed more than 6 months earlier. History of hypervascular HCC, presence of a hypointense hypovascular nodule in previous hepatocyte-phase MR images, percent prothrombin time, platelet count, serum levels of albumin, total bilirubin, aspartate aminotransferase, alanine aminotransferase, α-fetoprotein, and protein induced by vitamin K absence-II (PIVKA-II) were variables evaluated by multivariate logistic regression analysis. Multivariate analysis revealed that serum albumin level (odds ratio [95% confidence interval], 0.19 [0.06-0.57]; P = 0.0024), history of hypervascular HCC (8.62 [2.71-32.8]; P = 0.0001), and presence of a hypointense hypovascular nodule (4.18 [1.18-17.2]; P = 0.0256) were significant risk factors for hypervascular HCC. Patients with chronic liver disease showing a hypointense hypovascular nodule in the liver on hepatocyte-phase EOB-MRI have a high risk of HCC development.

Natural Course of Hypovascular Nodules Detected on Gadoxetic Acid-enhanced MR Imaging: Presence of Fat is a Risk Factor for Hypervascularization

Hypovascular nodules that exhibit hypointensity in hepatocyte-phase images of gadoxetic acid-enhanced magnetic resonance (MR) imaging are frequently encountered in clinical practice. We investigated risk factors for the development of these nodules into hypervascular hepatocellular carcinoma (HCC). We retrospectively reviewed our institutional database and identified 302 patients who underwent gadoxetic acid-enhanced MR imaging for suspected or confirmed HCC from February 1, 2008 to January 30, 2011. We excluded patients who were examined for metastasis of other malignancies or for other hepatic tumors, such as focal nodular hyperplasia. We identified hypovascular nodules that were hypointense in hepatocyte-phase images, recorded their characteristics, and calculated the cumulative hypervascularization rate for nodules that were followed up. Of the 302 patients, 82 had hypovascular nodules (178 nodules; mean size, 9.3 mm). Sixty nodules were followed up for over 6 months, and eight progressed to hypervascular HCC. Hypervascularization occurred more frequently in nodules with fat than those without (P<0.01). The cumulative hypervascularization rate was 5.1% over a year. The presence of intralesional fat was found to be a risk factor for hypervascularization of hypovascular nodules that exhibited hypointensity in the hepatocyte-phase images of gadoxetic acid-enhanced MR imaging.

CT prediction of histological grade of hypervascular hepatocellular carcinoma: utility of the portal phase

To elucidate whether the attenuation of hypervascular hepatocellular carcinoma (HCC) on the portal phase of dynamic CT is correlated with histological grade. This study group consisted of 66 patients with 74 surgically resected, hypervascular HCCs. On a preoperative dynamic study with a 64-multidetector row CT, the portal phase was scanned 60 s after injecting the contrast agent following the pre-contrast image and hepatic arterial phase. The tumor attenuation of each HCC on the portal phase was categorized into high, iso-, or low, and was compared with the predominant histological grade using Mann-Whitney's U test. Twenty-nine, 29, and 16 HCCs showed high, iso-, and low attenuation on the portal phase, respectively. Tumors were classified into three well- (w-), 58 moderately (m-), or 13 poorly (p-) differentiated HCCs. The tumor attenuation of p-HCC on the portal phase was significantly lower than those of w-HCC and m-HCC (p < 0.05 and p < 0.00001). The tumor attenuation on the portal phase may help when diagnosing the histological grade of hypervascular HCC. p-HCC are considered to show a faster contrast washout than w-HCC and m-HCC.

Risk of hypervascularization in small hypovascular hepatic nodules showing hypointense in the hepatobiliary phase of gadoxetic acid-enhanced MRI in patients with chronic liver disease

The purpose of this study was to elucidate the incidence and risk factors for the progression of hypointense nodules observed in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA-enhanced MRI) of hypervascular hepatocellular carcinoma (HCC). Hypovascular nodules (112) showing hypointensity in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI were examined in 54 patients. All patients underwent computed tomography during hepatic arteriography and computed tomography during arterial portography (CTAP) within a month after Gd-EOB-DTPA-enhanced MRI. According to the tumor size, 112 nodules were divided into two groups: those >10 mm in diameter (group A, n = 39) and those ≤10 mm in diameter (group B, n = 73). The incidence of progression to hypervascular HCC was calculated using the Kaplan-Meier method. The incidence of hypervascularization was significantly higher in group A nodules than in group B nodules (p < 0.0001). Tumor size (p < 0.0001) and hypoattenuation in CTAP (p = 0.0004) showed significant correlation with hypervascularization. Hypointense nodules observed in the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI with diameters of >10 mm had a high probability of hypervascularization.

Hypovascular Hypointense Nodules on Hepatobiliary Phase Gadoxetic Acid–enhanced MR Images in Patients with Cirrhosis: Potential of DW Imaging in Predicting Progression to Hypervascular HCC

To investigate the imaging features of hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced magnetic resonance (MR) images in patients with cirrhosis that may be associated with progression to hypervascular hepatocellular carcinoma (HCC). The institutional review board approved this retrospective study and waived informed patient consent. This study included 135 patients with a diagnosis of hepatitis B-induced liver cirrhosis and 214 hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced MR images. MR images were analyzed with respect to nodule size, degree of hypointensity at hepatobiliary phase (four grades), presence of fat, and signal intensity on T1- and T2-weighted and diffusion-weighted (DW) images. Univariate and multivariate Cox regression analyses were used to identify variables that are associated with developing hypervascular HCC. On follow-up MR images, 139 nodules (65.0%) had no evidence of HCC (mean follow-up, 522 days) (group 1), but 75 (35.0%) became hypervascular HCC (mean follow-up, 388 days) (group 2). Univariable Cox analysis revealed that the degree of hypointensity on hepatobiliary phase images (P=.044 and .001) and hyperintensity on T2-weighted and DW images (P=.001 and .0001) was significantly related to the development of hypervascular HCC. According to the multivariable Cox analysis, no other variable significantly adjusted the model once hyperintensity at initial DW imaging was already included as an associated variable, (hazard ratio, 7.44; 95% confidence interval: 4.28, 12.94; P=.0001). Hyperintensity on DW images in hypovascular hypointense nodules on hepatobiliary phase gadoxetic acid-enhanced MR images in patients with cirrhosis is strongly associated with progression to hypervascular HCC.