Hepatocelluar nodules in liver cirrhosis: hemodynamic evaluation (angiography-assisted CT) with special reference to multi-step hepatocarcinogenesis

To understand the hemodynamics of hepatocellular carcinoma (HCC) is important for the precise imaging diagnosis and treatment, because there is an intense correlation between their hemodynamics and pathophysiology. Angiogenesis such as sinusoidal capillarization and unpaired arteries shows gradual increase during multi-step hepatocarcinogenesis from high-grade dysplastic nodule to classic hypervascular HCC. In accordance with this angiogenesis, the intranodular portal supply is decreased, whereas the intranodular arterial supply is first decreased during the early stage of hepatocarcinogenesis and then increased in parallel with increasing grade of malignancy of the nodules. On the other hand, the main drainage vessels of hepatocellular nodules change from hepatic veins to hepatic sinusoids and then to portal veins during multi-step hepatocarcinogenesis, mainly due to disappearance of the hepatic veins from the nodules. Therefore, in early HCC, no perinodular corona enhancement is seen on portal to equilibrium phase CT, but it is definite in hypervascular classical HCC. Corona enhancement is thicker in encapsulated HCC and thin in HCC without pseudocapsule. To understand these hemodynamic changes during multi-step hepatocarcinogenesis is important, especially for early diagnosis and treatment of HCCs

肝細胞癌の分子・遺伝子的亜分類に基づいたradiogenomics

金沢大学附属病院放射線科肝細胞癌のうち予後良好な亜型であるβ-catenin活性化型では、hepatocyte nuclear factor4αの共発現がある場合にOATP1B3の発現が増加し、Gd-EOB-DTPA造影MRI肝細胞相での増強率の上昇が認められた。またP53変異型肝細胞癌では血清腫瘍マーカーが高値で組織学的に低分化型が多く、術後生存率が低いことから、悪性度の高い亜型と考えられた。画像所見の特徴として、dynamic CT動脈相での腫瘍内の拡張した動脈構造、EOB-MRI肝細胞相における腫瘍/肝信号強度比の低下が有意に認められた。β-catenin activated HCC showed increased enhancement ratio in the hepatobiliary phase of Gd-EOB-DTPA enhanced MRI in case of co-expression of hepatocyte nuclear factor (HNF) 4α. Co-expression of β-catenin and HNF4α would be the main mechanism inducing both OATP1B3 expression and less aggressive biological natures in this subtype of HCC.P53 mutated HCC showed significantly higher level of serum tumor markers, poorer differentiation grade and poorer survival rate after resection. Imaging features of intra-tumoral dilated arteries in the arterial phase of dynamic CT, and low signal intensity ratio in the hepatobiliary phase of EOB-MRI would be the independent predictors of this aggressive subtype.研究課題/領域番号:17K10354, 研究期間(年度):2017-04-01 - 2020-03-31出典：「肝細胞癌の分子・遺伝子的亜分類に基づいたradiogenomics」研究成果報告書　課題番号17K10354（KAKEN：科学研究費助成事業データベース（国立情報学研究所））（https://kaken.nii.ac.jp/report/KAKENHI-PROJECT-17K10354/17K10354seika/)を加工して作

肝細胞癌のGd-EOB-DTPA造影MRIによるsubtype分類

金沢大学附属病院肝細胞癌において、肝特異性MRI造影剤Gd-EOB-DTPAはトランスポーターOATP8により細胞に取り込まれる。肝細胞癌ではOATP8の発現低下によりGd-EOB-DTPA造影MRI肝細胞相で通常低信号を示すが、10-15％の頻度でOATP8の発現が亢進し高信号を示す一群が存在する。我々はこのような信号強度の差が特定の分子病理学的背景を有するsubtypeの違いを反映していると推測し、その生物学的特徴の比較検討を行った。その結果、高信号肝癌は低信号肝癌と比較して悪性度が低く予後良好な一群であり、マーカー発現パターンより成熟肝細胞に近い性質を有するsubtypeである可能性が示された。On the hepatobiliary phase of Gd-EOB-DTPA enhanced MR imaging (EOB-MRI), hepatocellular carcinoma (HCC) commonly shows hypointensity, however, a part of HCCs demonstrates hyperintensity caused by over-expression of OATP8, the uptake transporter of Gd-EOB-DTPA. We analyzed the correlation between the biological features and signal intensity on EOB-MRI in surgically resected HCC.Hyperintense HCC showed significantly less malignant biological features and better prognosis than those of hypointense HCC. Hyperintense HCC, namely OATP8 over-expressed HCC, is supposed to be a subtype with mature hepatocyte like molecular backgrounds.研究課題/領域番号:24791281, 研究期間(年度):2012-04-01 – 2014-03-3

Imaged periductal infiltration: Diagnostic and prognostic role in intrahepatic mass-forming cholangiocarcinoma

Purpose: This study examines periductal infiltration in intrahepatic mass-forming cholangiocarcinoma (IMCC), focusing on its importance for differentiating hepatic tumors and its influence on post-surgical survival in IMCC patients. Methods: Eighty-three consecutive patients with IMCC (n = 43) and liver cancer whose preoperative images showed intrahepatic bile duct dilatation adjacent to the tumor for differential diagnosis from hepatocellular carcinoma (HCC) [n = 21], metastatic liver cancer (MLC) [n = 16] and combined hepatocellular-cholangiocarcinoma (cHCC-CC) [n = 3] were enrolled. CT and MRI findings of simple bile duct compression, imaged periductal infiltration, and imaged intrabiliary growth adjacent to the main tumor were reviewed. Clinicopathological and imaging features were compared in each group. The sensitivity, specificity, and odds ratio were calculated for each imaging finding of IMCC versus the other tumor groups. Overall survival was compared between cases of IMCC with and without imaged periductal infiltration. Results: Simple bile duct compression and imaged intrabiliary growth were more frequently observed in HCC than in the others (p < 0.0001 and 0.040, respectively). Imaged periductal infiltration was observed more often in histopathologically confirmed large-duct type IMCC than in the small-duct type IMCC (p = 0.034). Multivariable analysis demonstrated that only imaged periductal infiltration (odds ratio, 50.67) was independently correlated with IMCC. Patients with IMCC who had imaged periductal infiltration experienced a poorer prognosis than those without imaged periductal infiltration (p = 0.0034). Conclusion: Imaged periductal infiltration may serve as a significant marker for differentiating IMCC from other liver cancers. It may also have the potential to predict post-surgical outcomes in patients with IMCC

Evaluation of renal oxygen saturation using photoacoustic imaging for the early prediction of chronic renal function in a model of ischemia-induced acute kidney injury.

PURPOSE:To evaluate the utility of photoacoustic imaging in measuring changes in renal oxygen saturation after ischemia-induced acute kidney injury, and to compare these measurements with histological findings and serum levels of kidney function. MATERIAL AND METHODS:Acute kidney injury was induced by clamping the left renal pedicle in C57Bl/6 mice, with a 35-min ischemic period used to induce mild renal injury (14 mice) and a 50-min period for severe injury (13 mice). The oxygen saturation was measured before induction, and at 5 time-points over the first 48 h after induction, starting at 4 h after induction. Oxygen saturation, histological score, kidney volume, and the 24 h creatinine clearance rate and serum blood urea nitrogen were also measured on day 28. Between-group differences were evaluated using a Mann-Whitney U-test and Dunn's multiple comparisons. The association between oxygen saturation and measured variables was evaluated using Spearman's correlation. A receiver operator characteristic curve was constructed from oxygen saturation values at 24 h after heminephrectomy to predict chronic renal function. RESULTS:The oxygen saturation was higher in the mild than severe renal injury group at 24 h after induction (73.7% and 66.9%, respectively, P<0.05). Between-group comparison on day 28 revealed a higher kidney volume (P = 0.007), lower tubular injury (P<0.001), lower serum level of blood urea nitrogen level (P = 0.016), and lower 24 h creatinine clearance rate (P = 0.042) in the mild compared with the severe injury group. The oxygen saturation at 24 h correlated with the 24 h creatinine clearance rate (P = 0.036) and serum blood urea nitrogen (P<0.001) on day 28, with an area under the receiver operating curve of 0.825. CONCLUSION:Oxygen saturation, measured by photoacoustic imaging at 24 h after acute kidney injury can predict the extent of subsequent histological alterations in the kidney early after injury

Hepatitis C Related Chronic Liver Cirrhosis: Feasibility of Texture Analysis of MR Images for Classification of Fibrosis Stage and Necroinflammatory Activity Grade

<div><p>Purpose</p><p>To assess the feasibility of texture analysis for classifying fibrosis stage and necroinflammatory activity grade in patients with chronic hepatitis C on T2-weighted (T2W), T1-weighted (T1W) and Gd-EOB-DTPA-enhanced hepatocyte-phase (EOB-HP) imaging.</p><p>Materials and methods</p><p>From April 2008 to June 2012, MR images from 123 patients with pathologically proven chronic hepatitis C were retrospectively analyzed. Texture parameters derived from histogram, gradient, run-length matrix, co-occurrence matrix, autoregressive model and wavelet transform methods were estimated with imaging software. Fisher, probability of classification error and average correlation, and mutual information coefficients were used to extract subsets of optimized texture features. Linear discriminant analysis in combination with 1-nearest neighbor classifier (LDA/1-NN) was used for lesion classification. In compliance with the software requirement, classification was performed based on datasets from all patients, the patient group with necroinflammatory activity grade 1, and that with fibrosis stage 4, respectively.</p><p>Results</p><p>Based on all patient dataset, LDA/1-NN produced misclassification rates of 28.46%, 35.77% and 20.33% for fibrosis staging and 34.15%, 25.20% and 28.46% for necroinflammatory activity grading in T2W, T1W and EOB-HP images. In the patient group with necroinflammatory activity grade 1, LDA/1-NN yielded misclassification rates of 5.00%, 0% and 12.50% for fibrosis staging in T2W, T1W and EOB-HP images respectively. In the patient group with fibrosis stage 4, LDA/1-NN yielded misclassification rates of 5.88%, 12.94% and 11.76% for necroinflammatory activity grading in T2W, T1W and EOB-HP images respectively.</p><p>Conclusion</p><p>Texture quantitative parameters of MR images facilitate classification of the fibrosis stage as well as necroinflammatory activity grade in chronic hepatitis C, especially after categorizing the input dataset according to the activity or fibrosis degree in order to remove the interference between the fibrosis stage and necroinflammatory activity grade on texture features.</p></div

Discrimination of necroinflammatory activity grades based on all patient dataset.

<p>Misclassification rates were 34.15%, 25.20% and 28.46% in T2W <b>(A)</b>, T1W <b>(B)</b> and EOB-HP <b>(C)</b> images, respectively. The three-dimensional distribution of data vectors is based on the top three of the 30 texture features that were extracted using Fisher+POE+ACC+MI method, following by LDA/1-NN classification: necroinflammatory activity grade 1 (1), grade 2 (2) and grade 3 (3). MDF1 and MDF 2 are the most discriminating features axes used in LDA to represent the classification graphically.</p

Discrimination of fibrosis stages based on patient group with necroinflammatory activity grade 1.

<p>Misclassification rates were 5.00%, 0% and 12.50% in T2W <b>(A)</b>, T1W <b>(B)</b> and EOB-HP <b>(C)</b> images, respectively. The three-dimensional distribution of data vectors is based on the top three of the 30 texture features that were extracted using Fisher+POE+ACC+MI method, followed by LDA/1-NN classification: fibrosis stage 1 (1), stage 2 (2), stage 3 (3), and stage 4 (4). MDF1, MDF 2 and MDF 3 are the most discriminating features axes used in LDA to represent the classification graphically.</p

Discrimination of fibrosis stages based on all patient dataset.

<p>Misclassification rates were 28.46%, 35.77% and 20.33% in T2W <b>(A)</b>, T1W <b>(B)</b> and EOB-HP <b>(C)</b> images, respectively. The three-dimensional distribution of data vectors is based on the top three of the 30 texture features that were extracted using Fisher coefficients + classification error probability combined with average correlation coefficients + mutual information coefficients (Fisher+POE+ACC+MI) methods, followed by linear discrimination analysis /1-nearest neighbor (LDA/1-NN) classification: fibrosis stage 1 (1), stage 2 (2), stage 3 (3), and stage 4 (4). Most discriminating factor1 (MDF1), MDF 2 and MDF 3 are the most discriminating feature axes used in LDA to represent the classification graphically.</p