3D CNN-based Deep Learning Model-based Explanatory Prognostication in Patients with Multiple Myeloma using Whole-body MRI.

Although magnetic resonance imaging (MRI) data of patients with multiple myeloma (MM) are used to predict prognosis, few reports have applied artificial intelligence (AI) techniques for this purpose. We aimed to analyze whole-body diffusion-weighted MRI data using three-dimensional (3D) convolutional neural networks (CNNs) and Gradient-weighted Class Activation Mapping (Grad-CAM), an explainable AI, to predict prognosis and explore the factors involved in prediction. We retrospectively analyzed the MRI data of a total of 142 patients with MM obtained from two medical centers. We defined the occurrence of progressive disease after MRI evaluation within 12 months as a poor prognosis and constructed a 3D CNN-based deep learning model to predict prognosis. Images from 111 cases were used as the training and internal validation data; images from 31 cases were used as the external validation data. Internal validation of the AI model with stratified 5-fold cross-validation resulted in a significant difference in progression-free survival (PFS) between good and poor prognostic cases (2-year PFS, 91.2% versus [vs.] 61.1%, P = 0.0002). The AI model clearly stratified good and poor prognostic cases in the external validation cohort (2-year PFS, 92.9% vs. 55.6%, P = 0.004), with an area under the receiver operating characteristic curve of 0.804. According to Grad-CAM, the MRI signals of the spleen and bones of the vertebrae and pelvis contributed to prognosis prediction. This study is the first to show that image analysis of whole-body MRI using a 3D CNN without any other clinical data is effective in predicting the prognosis of patients with MM.

Dynamic CT and Gadoxetic Acid-enhanced MRI Characteristics of P53-mutated Hepatocellular Carcinoma.

Background Imaging markers of hepatocellular carcinoma (HCC) on the basis of molecular classification are important for predicting malignancy grade and prognosis. P53-mutated HCC is a major aggressive subtype; however, its imaging characteristics have not been clarified. Purpose To clarify the imaging characteristics of P53-mutated HCC at dynamic CT and gadoxetic acid-enhanced MRI that are correlated with its clinical features, pathologic findings, and prognosis. Materials and Methods In this retrospective single-center study, patients with surgically resected HCC between January 2015 and May 2018 in a university hospital were evaluated. HCC was classified into P53-mutated HCC and non-P53-mutated HCC using immunostaining. Dynamic CT and gadoxetic acid-enhanced MRI findings, clinical features, pathologic findings, and prognosis were compared using Mann-Whitney test, χ2 test, multivariable regression analysis, receiver operating characteristic analysis, Kaplan-Meier method, and log-rank test. Immunohistochemical expression of P53, organic anion transporting polypeptide 1B3 (OATP1B3), and CD34 were evaluated, and the correlations were analyzed using the Pearson correlation test. Results In total, 149 patients (mean age, 67 years ± 9 [SD]; 103 men) with 173 HCCs were evaluated. P53-mutated HCC (n = 28) demonstrated higher serum α-fetoprotein (median, 127.5 ng/mL vs 5.5 ng/mL; P < .001), larger size (40.4 mm ± 29.7 vs 26.4 mm ± 20.5; P = .001), and higher rates of poorly differentiated HCC (22 of 28 [79%] vs 24 of 145 [17%]; P < .001). Dilated vasculature in the arterial phase of dynamic CT (odds ratio, 14; 95% CI: 3, 80; P = .002) and a lower relative enhancement ratio in the hepatobiliary phase (odds ratio, 0.05; 95% CI: 0.01, 0.34; cutoff value, 0.69; P = .002) independently predicted P53-mutated HCC. OATP1B3 expression and P53 expression were inversely correlated (P = .002; R = -0.24). Five-year overall survival was worse for P53-mutated HCC (50.0% vs 72.6%; P = .02). Conclusion Dilated vasculature at the arterial phase of dynamic CT and a lower relative enhancement ratio at the hepatobiliary phase of gadoxetic acid-enhanced MRI were useful markers for P53-mutated hepatocellular carcinoma with poor prognosis. © RSNA, 2022 Online supplemental material is available for this article.

Computer-Aided Detection of Subsolid Nodules on Chest Computed Tomography: Assessment of Visualization on Vessel-Suppressed Images.

OBJECTIVES: This study aimed to clarify the performance of automatic detection of subsolid nodules by commercially available software on computed tomography (CT) images of various slice thicknesses and compare it with visualization on the accompanying vessel-suppression CT (VS-CT) images. METHODS: A total of 95 subsolid nodules from 84 CT examinations of 84 patients were included. The reconstructed CT image series of each case with 3-, 2-, and 1-mm slice thicknesses were loaded into a commercially available software application (ClearRead CT) for automatic detection of subsolid nodules and generation of VS-CT images. Automatic nodule detection sensitivity was assessed for 95 nodules on each series of images acquired at 3 slice thicknesses. Four radiologists subjectively evaluated visual assessment of the nodules on VS-CT. RESULTS: ClearRead CT automatically detected 69.5% (66/95 nodules), 68.4% (65/95 nodules), and 70.5% (67/95 nodules) of all subsolid nodules in 3-, 2-, and 1-mm slices, respectively. The detection rate was higher for part-solid nodules than for pure ground-glass nodules at all slice thicknesses. In the visualization assessment on VS-CT, 3 nodules at each slice thickness (3.2%) were judged as invisible, while 26 of 29 (89.7%), 27 of 30 (90.0%), and 25 of 28 (89.3%) nodules, which were missed by computer-aided detection, were judged as visible in 3-, 2-, and 1-mm slices, respectively. CONCLUSIONS: The automatic detection rate of subsolid nodules by ClearRead CT was approximately 70% at all slice thicknesses. More than 95% of subsolid nodules were visualized on VS-CT, including nodules undetected by the automated software. Computed tomography acquisition at slices thinner than 3 mm did not confer any benefits.

Desmoid-type fibromatosis: imaging features and course.

Desmoid-type fibromatosis (DF) is a soft tissue tumor characterized by infiltrative growth and a tendency toward local recurrence, while it exhibits self-limiting behavior and shows spontaneous regression. With its unpredictable behavior, a change in treatment strategies from initial surgery to nonsurgical management has been proposed, and active surveillance is currently widely chosen as the initial treatment strategy for DF. We reviewed the imaging features of DF regarding its clinical course, focusing on regression cases, postoperative cases, and imaging changes after systemic treatment.

Single-Center Analysis of Pegfilgrastim-induced Aortitis Using a Drug Prescription Database and CT Findings.

Background Pegfilgrastim-induced aortitis is a rare but serious adverse event in patients undergoing anticancer therapy with granulocyte colony-stimulating factor analogs. Despite previous case series and systemic reviews, the exact incidence, clinical presentation, and CT manifestations of pegfilgrastim-induced aortitis remain unclear. Purpose To clarify the incidence and clinicoradiologic characteristics of pegfilgrastim-induced aortitis. Materials and Methods Pegfilgrastim administration records from January 2015 to March 2021 were retrospectively collected from the drug prescription database of a single center and were matched with the relevant findings in the CT database. Corresponding CT images within 6 months were available for a total of 1462 doses of pegfilgrastim in 674 patients. Four radiologists reviewed the CT images for the presence of aortitis in two steps. Clinical information and the distribution of aortitis on CT images were examined for patients with a diagnosis of pegfilgrastim-induced aortitis. Results Pegfilgrastim-induced aortitis was observed in 18 of 674 patients (mean age, 62 years ± 13 [SD]; 424 men), resulting in incidence rates of 2.7% per patient (95% CI: 1.6, 4.2) and 1.2% per dose (95% CI: 0.7, 1.9). The most common original primary malignancies were esophageal cancer (n = 10, 9%), breast cancer (n = 3, 4%), and pancreatic cancer (n = 2, 2%). The most common anticancer drugs used at onset were 5-fluorouracil, cisplatin, and docetaxel. Seven cases were symptomatic, while the remaining 11 (61%) were asymptomatic. CT findings indicated that aortitis involved branches of the aortic arch in 13 cases (72%), aortic arch in 10 cases (56%), and abdominal aorta in two cases (11%). Conclusion Pegfilgrastim-induced aortitis may be more prevalent than previously reported and may be more common in patients with esophageal cancer and those who received 5-fluorouracil, cisplatin, and docetaxel as anticancer drugs. The findings also suggest that pegfilgrastim-induced aortitis is often characterized by aortic arch and proximal branch involvement at CT. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Krinsky in this issue.

CT-diagnosed extra-pancreatic extension of pancreatic ductal adenocarcinoma is a more reliable prognostic factor for survival than pathology-diagnosed extension.

OBJECTIVES: To determine the correlation between CT-diagnosed extra-pancreatic extension of pancreatic ductal adenocarcinoma (PDAC), pathology-diagnosed extra-pancreatic extension, and survival in patients with PDAC. METHODS: This retrospective study included 87 patients with resected PDAC. Two radiologists evaluated negative ((i) tumours surrounded by the pancreatic parenchyma and (ii) tumours contacting the pancreatic surface) or positive ((iii) tumours with peri-pancreatic strand appearances and/or with expansive growth) CT-diagnosed extra-pancreatic extension. Clinical, pathological, and CT imaging characteristics predicting disease-free survival (DFS) and overall survival (OS) were assessed using Cox proportional-hazards models. Diagnostic accuracy for pathology-diagnosed extra-pancreatic extension was also assessed. RESULTS: CT-diagnosed extra-pancreatic extension (42/87 tumours, 48.3%; κ = 0.82) had a higher hazard ratio (HR) for the DFS (HR, 5.30; p < 0.01) and OS (HR, 5.31; p < 0.01) rates than pathology-diagnosed extension in univariable analyses. It was also an independent prognostic factor for the DFS (HR, 4.22; p < 0.01) and OS (HR, 4.38; p < 0.01) rates in multivariable analyses. Of 45 tumours without CT-diagnosed extra-pancreatic extension, pathology-diagnosed extra-pancreatic extension was observed in 2/8 (25.0%) and 32/37 (86.5%) tumours with CT categories (i) and (ii), respectively. However, the differences in the survival rates between patients with CT categories (i) and (ii) were insignificant, although those in the latter category had significantly better survival rates than those with CT-diagnosed extra-pancreatic extension (category (iii)). CONCLUSIONS: CT-diagnosed extra-pancreatic extension was a better prognostic factor than pathology-diagnosed extension and considered an independent factor for the postoperative DFS and OS rates with reasonable frequency and high reproducibility, despite the low diagnostic accuracy for predicting pathology-diagnosed extra-pancreatic extension. KEY POINTS: • A CT-diagnosed extra-pancreatic extension had a higher hazard ratio for both disease-free survival and overall survival compared to pathology-diagnosed extension in univariable survival analyses. • A CT-diagnosed extra-pancreatic extension was a significant independent predictor of both disease-free survival and overall survival, as observed in multivariable survival analyses. • Patients with tumours contacting with the pancreatic surface on CT images (CT category (ii)) showed similar survival rates to those whose tumours were surrounded by the pancreatic parenchyma (CT category (i)), although many tumours with CT category (ii) extended pathologically beyond the pancreas.

Ultrasonography of IgG4-related dacryoadenitis and sialadenitis: Imaging features and clinical usefulness.

OBJECTIVES: To clarify the ultrasonographic features of immunoglobulin G4 (IgG4)-related dacryoadenitis and sialadenitis (IgG4-DS) and their usefulness in clinical diagnostic sessions. METHODS: By re-evaluating 96 consecutive patients with IgG4-related disease, we identified 54 patients (male:female = 37:17; median age, 69.5 years) who underwent lacrimal or submandibular gland (LG or SG, respectively) ultrasonography and computed tomography (CT). Their clinical and ultrasonographic features were retrospectively analysed. Radio-pathological correlations were also examined in LG (23 cases) and SG lesions (20 cases). Additionally, the diagnostic accuracy of CT for LG/SG lesions was evaluated. RESULTS: Abnormal ultrasonographic findings were detected in 33 (LGs) and 38 (SGs) patients, and most of them were observed bilaterally. All lesions were well demarcated and demonstrated diffuse low-echoic areas (rocky pattern) or multiple low-echoic nodules surrounded by high-echoic linear shadows (cobblestone pattern) corresponding to intra-lobular inflammation and inter-lobular fibrosis. Moreover, 42% (LGs; 14/33) and 42% (SGs; 16/38) patients had glandular lesions without clinical symptoms associated with the affected glands. The diagnostic accuracy of CT was ∼80% for LG and 55% for SG. CONCLUSIONS: Ultrasonographic findings in IgG4-DS included diffuse or nodular low-echoic areas with linear high-echoic structures corresponding to inflamed lobules and inter-lobular fibrosis. These findings can help detect IgG4-DS.

Pulmonary Vascular Alterations on Computed Tomography Imaging and Outcomes in Heart Failure With Preserved Ejection Fraction: a Preliminary Data.

BACKGROUND: Pulmonary vascular disease may play an important role in the pathophysiology of heart failure (HF) with preserved ejection fraction (HFpEF). However, no study has demonstrated noninvasive quantification of pulmonary vascular alterations in HFpEF. This study sought to determine the association between pulmonary vascular alterations quantified by chest computed tomography scan and clinical outcomes in HFpEF. METHODS AND RESULTS: Pulmonary vascular alterations were quantified in 151 patients with HFpEF who underwent noncontrast chest computed tomography scan by measuring the percentage of total cross-sectional area (CSA) of pulmonary vessels less than 5 mm2 to the total lung area (%CSA<5). We divided the patients by the median value of %CSA<5 (=1.45%) and examined the association between %CSA<5 and a composite outcome of all-cause mortality or HF hospitalization. During a median follow-up of 17.3 months, there were 44 (29%) composite outcomes. Event rates were significantly higher in patients with higher %CSA<5 than those with lower %CSA<5 (log-rank P = .02). %CSA<5 was associated with an increased risk of the outcome (hazard ratio per 1.0% increment, 1.46; 95% confidence interval 1.06-1.98; P = .02) in an unadjusted Cox model, and was independently and incrementally associated with the outcome over age, the presence of atrial fibrillation, E/e' ratio, and estimated pulmonary artery systolic pressure (global χ2 17.3 vs 11.5, P = .02). CONCLUSIONS: A higher %CSA<5 was associated with an increased risk of all-cause mortality or HF hospitalization in patients with HFpEF, with an incremental prognostic value over age, atrial fibrillation, E/e' ratio, and pulmonary artery systolic pressure.

Gadoxetic acid-enhanced MR imaging for hepatocellular carcinoma: molecular and genetic background.

Gadoxetic acid-enhanced magnetic resonance imaging (MRI) plays important roles in diagnosis of hepatic lesions because of its superiority in the detectability of small lesions, its differentiation ability, and its utility for the early diagnosis of hepatocellular carcinoma (HCC). In HCC, expression of organic anion transporting polypeptide (OATP) 1B3 correlates with the enhancement ratio in the hepatobiliary phase. Gadoxetic acid-enhanced MRI, an indirect molecular imaging method, reflects OATP1B3 expression in HCC. OATP1B3 expression gradually decreases from the dysplastic nodule stage to advanced HCC. Decreased expression is a sensitive marker of multistep hepatocarcinogenesis, especially in the early stages. Hypervascular HCCs commonly show hypointensity in the hepatobiliary phase corresponding to a decrease in OATP1B3; however, approximately 10% of HCCs show hyperintensity due to OATP1B3 overexpression. This hyperintense HCC shows less aggressive biological features and has a better prognosis than hypointense HCC. Hyperintense HCC can be classified into a genetic subtype of HCC with a mature hepatocyte-like molecular expression. OATP1B3 expression and the less aggressive nature of hyperintense HCC are regulated by the molecular interaction of ß-catenin signaling and hepatocyte nuclear factor 4α, a tumor suppressor factor. Gadoxetic acid-enhanced MR imaging has the potential to be an imaging biomarker for HCC. KEY POINTS: • The hepatobiliary phase is a sensitive indirect indicator of organic anion transporting polypeptide1B3 (OATP1B3) expression in hepatocellular carcinoma (HCC). • The OATP1B3 expression, namely, enhancement in the hepatobiliary phase, decreases from the very early stage of hepatocarcinogenesis, contributing to early diagnosis of HCC. • HCC showing hyperintensity on the hepatobiliary phase is a peculiar genetic subtype of HCC with OATP1B3 overexpression, a less aggressive nature, and mature hepatocyte-like molecular/genetic features.

Prostatic Remnant After Prostatectomy: MR Findings and Prevalence in Clinical Practice.

OBJECTIVE. The purpose of this article is to evaluate the MR findings of prostatic remnant after prostatectomy and estimate the prevalence of prostatic remnant in patients that undergo MRI after prostatectomy. MATERIALS AND METHODS. Sixty-six patients who had undergone radical prostatectomy with pathologically proven benign prostatic remnant between 2007 and 2017 were retrospectively reviewed. Pathologically proven benign prostatic remnant was determined on the basis of initial pathologic report. Of the 66 initial patients, 30 patients with biopsy-proven benign prostatic remnant without coexisting recurrent prostate carcinoma and three patients who underwent repeat resection for completion prostatectomy were enrolled. MRI characteristics including location, size, signal intensity on T2-weighted images and DWI, and contrast enhancement pattern were analyzed. Nine additional patients were found to have a prostatic remnant by imaging without biopsy. The prevalence of prostatic remnant among those undergoing MRI for suspected recurrence during the same period was estimated. RESULTS. Prostatic remnant was detected in 23 of 33 patients on MRI. The remaining 10 patients did not have any visible abnormality. The 23 detected lesions were located in three regions: under the vesicourethral anastomosis in five patients, in the bladder neck in 12 patients, and posterior to the bladder in six patients. On T2-weighted imaging, 17 of 23 lesions showed heterogeneous hyperintensity. On DWI, 14 lesions showed hyperintensity. Dedicated MRI studies were performed for suspected prostate cancer recurrence in 2466 patients during the same period. Prevalence of exclusively benign prostate remnant detectable on MRI was approximately 1% of that population (23/2466-35/2466), and overall prevalence of any prostate remnant detectable on MRI was 3% (75/2466). CONCLUSION. Benign prostate remnant after prostatectomy occurs at three common sites and typically shows heterogeneous hyperintensity on T2-weighted imaging. The prevalence of detectable prostatic remnant in men who undergo MRI for suspected recurrence was approximately 1-3%.

Doughnut-like hyperintense nodules on hepatobiliary phase without arterial-phase hyperenhancement in cirrhotic liver: imaging and clinicopathological features.

OBJECTIVES: To determine the imaging and clinicopathological features of MRI doughnut-like nodules (HBP-doughnut nodules), hyperintense at the hepatobiliary phase (HBP) after injection of gadoxetic acid (EOB) and without arterial-phase hyperenhancement (APHE) in cirrhotic liver. METHODS: The Institutional Review Board approved this retrospective study and informed consent was waived. We enrolled 309 consecutive patients with liver cirrhosis who were examined by EOB-MRI, dynamic CT, and angiography-assisted CT between 2008 and 2012 and searched for HBP-doughnut nodules. We evaluated imaging characteristics including haemodynamics and signal intensity of MRI, pathological findings, and frequency of malignant transformation. RESULTS: One hundred and one HBP-doughnut nodules without APHE were identified in 18 patients (6%), including seven of 59 (12%) patients with hepatitis-B-virus-related, nine of 230 (3.9%) with hepatitis-C-virus-related, and two of 33 (6.1%) with alcoholic cirrhosis. All nodules showed enhancement peaks in the portal phase, the same or increased intranodular portal supply on CT during arterial portography, and the same or decreased intranodular arterial supply on CT during hepatic arteriography. On T2-weighted and diffusion-weighted images, 37 (36%) and 24 (24%) nodules, respectively, showed hyperintensity predominantly in the central area. Three nodules were diagnosed by fine needle biopsy as non-neoplastic hepatic nodules. Ninety-three of 101 (92%) nodules in 16 patients were followed up during an observation period of 1163 ± 902 days (range 57-2920 days), and none showed malignant transformation. CONCLUSION: HBP-doughnut nodules without APHE in cirrhotic liver were not infrequent. None became malignant. We propose calling them 'multiacinar cirrhotic nodules' based on the classification by an International Working Party. KEY POINTS: • HBP-doughnut nodules without APHE were seen in 6% of patients with liver cirrhosis. • The enhancement peak of HBP-doughnut nodules without APHE was in the portal phase, which reflected the fact that they were supplied predominantly by the portal vein, based on angiography-assisted CT findings. • None of the HBP-doughnut nodules without APHE in cirrhotic liver became malignant, and in conjunction with limited pathological features, they may be corresponding to multiacinar cirrhotic nodules in the International Working Party classification.

Multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney: CT and MRI findings and clinical characteristic.

PURPOSE: The aim of this study was to clarify the radiologic and clinical characteristics of multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney. METHOD: Fourteen patients with unique and characteristic multiple hemorrhagic subcapsular cortical cysts of the kidney, not categorized in any existing renal cystic diseases, were retrospectively reviewed. The clinical information including age, sex, symptom, family history of renal or renal cystic disease, and laboratory data were collected. CT and MRI findings including distribution, number and size of cysts, and CT attenuation and signal intensity on T1- and T2-weighted MRI of cysts were analyzed. RESULTS: All patients except one were young and none had a family history of renal or renal cystic disease. Common clinical symptoms were flank or abdominal pain and hematuria. In all cases, only the left kidney was involved at initial presentation. Cysts were small (median cyst size, 4-15 mm), numerous, and distributed mainly along the subcapsular cortex of the kidney. Cysts were hyper-attenuated on unenhanced CT, extremely hypointense on T2-weighted MRI, and mildly hyperintense on T1-weighted MRI. All patients except one had normal renal function. Imaging follow-up revealed stable or mildly progressive disease in seven patients. Two patients developed several hemorrhagic subcapsular cortical cysts in the right kidney at follow-up. Three of five patients with a renal pathology specimen showed concurrent IgA nephropathy. CONCLUSION: We have identified a unique renal cystic disease with multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney that has a characteristic manifestation both radiologically and clinically. KEY POINTS: • Multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney is a unique non-familial renal cystic disease with a characteristic manifestation both radiologically and clinically. • Most cases of multiple unilateral subcapsular cortical hemorrhagic cystic disease of the kidney are stable or slowly progressive, and do not require invasive intervention.

CT Findings of Thoracic Paravertebral Lesions in IgG4-Related Disease.

OBJECTIVE. The objective of our study was to characterize the CT findings of IgG4-related paravertebral lesions. MATERIALS AND METHODS. We selected cases of IgG4-related paravertebral lesions that satisfied two inclusion criteria: first, lesions in patients with IgG4-related disease diagnosed by a multidisciplinary approach between April 2007 and June 2018; and, second, patients who had soft-tissue lesions in paravertebral regions on CT images. We added one case of an IgG4-related paravertebral lesion diagnosed pathologically in 2003. Finally, the study consisted of 30 patients (25 men and five women; median age, 69.5 years). We retrospectively evaluated the CT findings of the paravertebral lesions. RESULTS. A total of 31 paravertebral lesions were identified in 30 patients. All lesions were located around thoracic vertebrae, particularly the lower thoracic regions (n = 30). Twenty-six lesions (84%) involved two or more vertebrae in a row. The right side of vertebrae was predominantly affected in all cases except one (30/31 lesions). Radiologically, the paravertebral lesions were characterized as a bandlike, demarcated soft-tissue mass (mean maximum thickness, 8.7 mm) with homogeneous enhancement on late phase images of contrast-enhanced CT. All patients had IgG4-related lesions at other sites. Histologically, paravertebral lesions showed sclerosing inflammation consisting of diffuse lymphoplasmacytic infiltrations with many IgG4-positive plasma cells and irregular fibrosis. CONCLUSION. IgG4-related paravertebral lesions occur mainly in the right side of the lower thoracic vertebrae and present as a homogeneously enhanced bandlike mass corresponding to plasma cell-rich sclerosing inflammation.

Imaging and pathological features of gastric lesion of immunoglobulin G4-related disease: A case report and review of the recent literature.

We describe a 67-year-old man with immunoglobulin G4-related disease (IgG4-RD) presenting with optic neuropathy, dacryoadenitis, periaortitis, retroperitoneal fibrosis, and a gastric mass-like lesion. A mass-like lesion measuring 52 × 40 mm in the antrum of the stomach was found incidentally through whole-body screening for other organ involvement of IgG4-RD using contrast-enhanced computed tomography (CT). Histology of the stomach revealed that the lesion was also IgG4-related and was located in the submucosal layer extending to the subserosal region. This case suggests that the stomach can also be a site of involvement of IgG4-RD.

Isolated Arteries Originating from the Intrahepatic Arteries: Anatomy, Function, and Importance in Intervention.

Isolated hepatic arteries are defined as hepatic terminal arterioles that are not accompanied by portal venules or bile ductules and penetrate the liver parenchyma and distribute to the hepatic capsule and intrahepatic hepatic veins. Abundant communications exist between intra- and extrahepatic arteries through isolated arteries and capsular arterial plexus. They play a principal role in the development of subcapsular hemorrhage and arterial collateral formation following transcatheter arterial chemoembolization for liver cancers. The anatomy, function, and clinical importance of isolated hepatic arteries in interventional radiology, especially regarding subcapsular hemorrhage and arterial collateral formation, are highlighted in this article.

What Does Deep Learning See? Insights From a Classifier Trained to Predict Contrast Enhancement Phase From CT Images.

OBJECTIVE: Deep learning has shown great promise for improving medical image classification tasks. However, knowing what aspects of an image the deep learning system uses or, in a manner of speaking, sees to make its prediction is difficult. MATERIALS AND METHODS: Within a radiologic imaging context, we investigated the utility of methods designed to identify features within images on which deep learning activates. In this study, we developed a classifier to identify contrast enhancement phase from whole-slice CT data. We then used this classifier as an easily interpretable system to explore the utility of class activation map (CAMs), gradient-weighted class activation maps (Grad-CAMs), saliency maps, guided backpropagation maps, and the saliency activation map, a novel map reported here, to identify image features the model used when performing prediction. RESULTS: All techniques identified voxels within imaging that the classifier used. SAMs had greater specificity than did guided backpropagation maps, CAMs, and Grad-CAMs at identifying voxels within imaging that the model used to perform prediction. At shallow network layers, SAMs had greater specificity than Grad-CAMs at identifying input voxels that the layers within the model used to perform prediction. CONCLUSION: As a whole, voxel-level visualizations and visualizations of the imaging features that activate shallow network layers are powerful techniques to identify features that deep learning models use when performing prediction.

Gadoxetic acid-enhanced magnetic resonance imaging reflects co-activation of ß-catenin and hepatocyte nuclear factor 4α in hepatocellular carcinoma.

AIM: The aim of this study is to clarify the correlation of the co-activation of ß-catenin and hepatocyte nuclear factor (HNF)4α with the findings of gadoxetic acid-enhanced magnetic resonance imaging (MRI), organic anion transporting polypeptide (OATP)1B3 expression, and histological findings in hepatocellular carcinoma (HCC). METHODS: One hundred and ninety-six HCCs surgically resected from 174 patients were enrolled in this study. The HCCs were classified into four groups by immunohistochemical expression of ß-catenin, glutamine synthetase (GS), and HNF4α: (i) ß-catenin/GS (positive [+]) HNF4α (+); (ii) ß-catenin/GS (+) HNF4α (negative [-]); (iii) ß-catenin/GS (-) HNF4α (+); and (iv) ß-catenin/GS (-) HNF4α (-). We compared the four groups in terms of the enhancement ratio on the hepatobiliary phase of gadoxetic acid-enhanced MRI, immunohistochemical organic anion transporter polypeptide (OATP)1B3 (a main uptake transporter of gadoxetic acid) expression and histological features, overall survival, and no recurrence survival. The Kruskal-Wallis test, Steel-Dwass multiple comparisons test, Fisher's exact test, and log-rank (Mantel-Cox) test were used for statistical analyses. RESULTS: Enhancement ratio on gadoxetic acid-enhanced MRI in HCC with ß-catenin/GS (+) HNF4α (+) was significantly higher than those of the other three groups (P < 0.001). The OATP1B3 grade was also significantly higher in HCC with ß-catenin/GS (+) HNF4α (+) (P < 0.001). Hepatocellular carcinoma with ß-catenin/GS (+) HNF4α (+) showed the highest differentiation grade as compared to the other groups (P < 0.004). There were no significant differences in portal vein invasion, macroscopic growth pattern, or prognosis analyses between the four groups. CONCLUSION: Co-activation of ß-catenin and HNF4α would promote OATP1B3 expression, and consequently higher enhancement ratio on gadoxetic acid-enhanced MRI and higher differentiation grade in HCC.

Benign Hepatocellular Nodules: Hepatobiliary Phase of Gadoxetic Acid-enhanced MR Imaging Based on Molecular Background.

Gadoxetic acid is a contrast agent for magnetic resonance (MR) imaging with hepatocyte-specific properties and is becoming increasingly important in detection and characterization of hepatocellular carcinoma and benign hepatocellular nodules, including focal nodular hyperplasia (FNH), nodular regenerative hyperplasia (NRH), hepatocellular adenoma (HCA), and dysplastic nodule. In these hepatocellular nodules, a positive correlation between the grade of membranous uptake transporter organic anion-transporting polypeptide (OATP) 1B3 expression and signal intensity in the hepatobiliary (HB) phase has been verified. In addition, it has been clarified that OATP1B3 expression is regulated by activation of ß-catenin and/or hepatocyte nuclear factor 4α. On the other hand, recent studies have also revealed some of the background molecular mechanisms of benign hepatocellular nodules. FNH commonly shows iso- or hyperintensity in the HB phase with equal or stronger OATP1B3 expression, with map-like distribution of glutamine synthetase (a target of Wnt/ß-catenin signaling) and OATP1B3 expression. NRH shows doughnut-like enhancement with hypointensity in the central portion in the HB phase with OATP1B3 expression. The majority of HCAs show hypointensity in the HB phase, but ß-catenin-activated HCA exclusively demonstrates iso- or hyperintensity with increased expression of nuclear ß-catenin, glutamine synthetase, and OATP1B3. Dysplastic nodule commonly shows iso- or hyperintensity in the HB phase with similar to increased OATP1B3 expression, but one-third of high-grade dysplastic nodules can be demonstrated as a hypointense nodule with decreased OATP1B3 expression. Knowledge of these background molecular mechanisms of gadoxetic acid-enhanced MR imaging is important not only for precise imaging diagnosis but also understanding of the pathogenesis of benign hepatocellular nodules. ©RSNA, 2016.

Hepatocellular Carcinoma with ß-Catenin Mutation: Imaging and Pathologic Characteristics.

PURPOSE: To identify the imaging features of hepatocellular carcinoma (HCC) associated with ß-catenin mutation and their relationship to pathologic findings. MATERIALS AND METHODS: Institutional ethics committee approval and informed consent were obtained. One hundred thirty-eight surgically resected HCCs were analyzed in this study. Immunohistochemical expression of ß-catenin and its transcriptional product, glutamine synthetase (GS), were graded and classified into three groups: the ß-catenin positive and GS positive group (HCC with ß-catenin mutation), the ß-catenin negative and GS positive group (intermediate HCC), and the ß-catenin negative and GS negative group (HCC without ß-catenin mutation). Clinical, pathologic, and imaging findings from dynamic computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance (MR) imaging (T1-weighted, T2-weighted, diffusion-weighted, and hepatobiliary phase imaging) were evaluated. Correlations among immunohistochemical expression of ß-catenin, GS, and organic anion transporting polypeptide 1B3 (uptake transporter of gadoxetic acid) were evaluated. The χ(2), Kruskal-Wallis, and Spearman correlation tests were used. RESULTS: HCCs with ß-catenin mutation (n = 27) showed a lower median contrast-to-noise ratio at diffusion-weighted imaging than did intermediate HCCs (n = 23) and HCCs without ß-catenin mutation (n = 84) (13.2, 24.4, and 27.0, respectively; P = .02), higher apparent diffusion coefficient (1.33, 1.13, and 1.12, respectively; P < .0001), higher contrast-to-noise ratio (0.58, -28.7, and -45.0, respectively; P < .0001) and higher enhancement ratio during the hepatobiliary phase (0.90, 0.50, and 0.42, respectively; P < .0001). At pathologic examination, HCCs with ß-catenin mutation showed pseudoglandular proliferation and bile production with a higher grade of differentiation (P = .04, .001, and .005, respectively). There were significant positive correlations among expression of ß-catenin, GS, and organic anion transporting polypeptide 1B3 (P < .0001). CONCLUSION: HCCs with ß-catenin mutation showed a higher grade of differentiation with frequent pseudoglandular patterns and bile production, and characteristic imaging findings included a high enhancement ratio at gadoxetic acid-enhanced MR imaging and a high apparent diffusion coefficient at diffusion-weighted imaging. Online supplemental material is available for this article.

Correlation between Gd-EOB-DTPA-enhanced MR imaging findings and OATP1B3 expression in chemotherapy-associated sinusoidal obstruction syndrome.

We report a female case of sinusoidal obstruction syndrome (SOS) diagnosed pathologically after chemotherapy (Pmab+m-FOLFOX6) for ascending colon cancer with multiple liver metastases, focusing on the findings of gadoxetic acid-enhanced MRI (EOB-MRI) and the organic anion transporting polypeptide 1B3 (OATP1B3) expression of in the liver. The patient was a 75-year-old female. She had received chemotherapy (Pmab+m-FOLFOX6) as six cycles for preoperative chemotherapy. After the preoperative chemotherapy, tumor sizes of hepatic metastases were reduced and hepatobiliary phase of EOB-MRI clearly depicted diffuse reticular hypointensity in the background liver. On the other hand, dynamic CT and/or other sequences of EOB-MRI did not show definite abnormality in the background liver. After the operation, this patient was pathologically confirmed as SOS demonstrating centrilobular congestion, sinusoidal dilatation, and perisinusoidal fibrosis. In normal liver parenchyma, OATP1B3 (uptake transporter of the EOB-MRI) expression is observed predominantly in centrilobular hepatocytes (zone 3). On the other hand, OATP1B3 expression was remarkably reduced because of the damages in the centrilobular (zone 3) hepatocytes in this SOS case. This indicated that EOB-MRI might be extremely sensitive in diagnosing SOS in its early stage.